An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)
A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.
A biologic alkylating agent that exerts its cytotoxic effects by forming DNA ADDUCTS and DNA interstrand crosslinks, thereby inhibiting rapidly proliferating cells. The hydrochloride is an antineoplastic agent used to treat HODGKIN DISEASE and LYMPHOMA.
A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
Tumors or cancer of the SKIN.
An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)
Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms.
A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.
An alkylating agent of value against both hematologic malignancies and solid tumors.
One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.
The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.
A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.
An enzyme that transfers methyl groups from O(6)-methylguanine, and other methylated moieties of DNA, to a cysteine residue in itself, thus repairing alkylated DNA in a single-step reaction. EC 2.1.1.63.
Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
The sudden sensation of being cold. It may be accompanied by SHIVERING.
Organic salts and esters of benzenesulfonic acid.
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
6-carbon straight-chain or branched ketones.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.
Delivery of substances through VENIPUNCTURE into the VEINS.
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.
Compounds that include the amino-N-phenylamide structure.
An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Vinblastine derivative with antineoplastic activity against CANCER. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS).
Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.
Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.
Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
A nonparametric method of compiling LIFE TABLES or survival tables. It combines calculated probabilities of survival and estimates to allow for observations occurring beyond a measurement threshold, which are assumed to occur randomly. Time intervals are defined as ending each time an event occurs and are therefore unequal. (From Last, A Dictionary of Epidemiology, 1995)
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Therapeutic act or process that initiates a response to a complete or partial remission level.
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of EPINEPHRINE and NOREPINEPHRINE, is HYPERTENSION, which may be persistent or intermittent. During severe attacks, there may be HEADACHE; SWEATING, palpitation, apprehension, TREMOR; PALLOR or FLUSHING of the face, NAUSEA and VOMITING, pain in the CHEST and ABDOMEN, and paresthesias of the extremities. The incidence of malignancy is as low as 5% but the pathologic distinction between benign and malignant pheochromocytomas is not clear. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1298)

Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer. (1/1313)

The purpose of this study is to characterize the absorption, metabolism, and excretion of carbon 14-labeled temozolomide (14C-TMZ) administered p.o. to adult patients with advanced solid malignancies. On day 1 of cycle 1, six patients received a single oral 200-mg dose of 14C-TMZ (70.2 microCi). Whole blood, plasma, urine, and feces were collected from days 1-8 and on day 14 of cycle 1. Total radioactivity was measured in all samples. TMZ, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) concentrations were determined in plasma, and urine and plasma samples were profiled for metabolite/degradation products. Maximum TMZ plasma concentrations were achieved between 0.33 to 2 h (mean, 1.2 h), and half-life, apparent volume of distribution, and oral clearance values averaged 1.9 h, 17 liters/m2, and 104 ml/min/m2, respectively. A first-order absorption, one-compartment linear model, which included first-order formation of MTIC from TMZ and elimination of MTIC via degradation to AIC, and a peripheral distribution compartment for AIC, adequately described the plasma TMZ, MTIC, and AIC concentrations. MTIC systemic clearance was estimated to be 5384 ml/min/m2, and the half-life was calculated to be 2.5 min. Metabolite profiles of plasma at 1 and 4 h after treatment showed that 14C-derived radioactivity was primarily associated with TMZ, and a smaller amount was attributed to AIC. Profiles of urine samples from 0-24 h revealed that 14C-TMZ-derived urinary radioactivity was primarily associated with unchanged drug (5.6%), AIC (12%), or 3-methyl-2,3-dihydro-4-oxoimidazo[5,1-d]tetrazine-8-carboxyl ic acid (2.3%). The recovered radioactive dose (39%) was principally eliminated in the urine (38%), and a small amount (0.8%) was excreted in the feces. TMZ exhibits rapid oral absorption and high systemic availability. The primary elimination pathway for TMZ is by pH-dependent degradation to MTIC and further degradation to AIC. Incomplete recovery of radioactivity may be explained by the incorporation of AIC into nucleic acids.  (+info)

Interactive effects of inhibitors of poly(ADP-ribose) polymerase and DNA-dependent protein kinase on cellular responses to DNA damage. (2/1313)

DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP) are activated by DNA strand breaks and participate in DNA repair. We investigated the interactive effects of inhibitors of these enzymes [wortmannin (WM), which inhibits DNA-PK, and 8-hydroxy-2-methylquinazolin-4-one (NU1025), a PARP inhibitor] on cell survival and DNA double-strand break (DSB) and single-strand break (SSB) rejoining in Chinese hamster ovary-K1 cells following exposure to ionizing radiation (IR) or temozolomide. WM (20 microM) or NU1025 (300 microM) potentiated the cytotoxicity of IR with dose enhancement factors at 10% survival (DEF10) values of 4.5 +/- 0.6 and 1.7 +/- 0.2, respectively. When used in combination, a DEF10 of 7.8 +/- 1.5 was obtained. WM or NU1025 potentiated the cytotoxicity of temozolomide, and an additive effect on the DEF10 value was obtained with the combined inhibitors. Using the same inhibitor concentrations, their single and combined effects on DSB and SSB levels following IR were assessed by neutral and alkaline elution. Cells exposed to IR were post-incubated for 30 min to allow repair to occur. WM or NU1025 increased net DSB levels relative to IR alone (DSB levels of 1.29 +/- 0.04 and 1.20 +/- 0.05, respectively, compared with 1.01 +/- 0.03 for IR alone) and the combination had an additive effect. WM had no effect on SSB levels, either alone or in combination with NU1025. SSB levels were increased to 1.27 +/- 0.05 with NU1025 compared with IR alone, 1.02 +/- 0.04. The dose-dependent effects of the inhibitors on DSB levels showed that they were near maximal by 20 microM WM and 300 microM NU1025. DSB repair kinetics were studied. Both inhibitors increased net DSB levels over a 3 h time period; when they were combined, net DSB levels at 3 h were identical to DSB levels immediately post-IR. The combined use of DNA repair inhibitors may have therapeutic potential.  (+info)

Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. (3/1313)

PURPOSE: The combination of chemotherapy with immunotherapeutic agents such as interleukin-2 and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone. We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. PATIENTS AND METHODS: One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2. Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-up of 42 months. RESULTS: In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. In 50 patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy. CONCLUSION: With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.  (+info)

Combination of chemotherapy with interleukin-2 and interferon alfa for the treatment of metastatic melanoma. (4/1313)

PURPOSE: The primary objective of this clinical study was to assess the feasibility of administering recombinant interleukin-2 and recombinant interferon alfa-2a before and after combination cytotoxic chemotherapy. After encouraging initial responses, the study was expanded to further evaluate the therapeutic potential, clarify the toxicities of this regimen, and explore any associated immunologic changes. PATIENTS AND METHODS: Eighty-four patients with metastatic melanoma, including patients with brain metastases, were treated on this 6-week protocol. Patients received combination cisplatin (25 mg/m2/d) and dacarbazine (220 mg/m2/d) on days 1 through 3 and 22 through 24 plus carmustine (150 mg/m2) on day 1. Interleukin 2 (13.5 million IU/m2/d) and interferon alfa (6 MU/m2/d) were administered on days 4 through 8 and 17 through 21. RESULTS: Among 83 patients assessable for response, 12 complete and 34 partial responses were documented (55% response rate). The median time to disease progression was 7 months, the median survival from study entry was 12.2 months, and the median survival from diagnosis of metastatic disease was 15.5 months. Although patients were hospitalized to receive treatment, intensive care unit support generally was not needed. Dose-limiting toxicities were related to elevations in serum bilirubin and serum creatinine levels. No patient developed a grade 4 clinical toxicity. Treatment produced a skin depigmentation, which was associated with prolonged survival. CONCLUSION: A plateau in both the survival and time to progression curves beyond 2 years (15% of the patients) and a greater than 10% disease-free survival beyond 4 years indicate that there may be a long-term benefit for some patients. The limited toxicity of this regimen should permit its use in most oncology settings. A randomized trial of chemoimmunotherapy versus chemotherapy should be performed to establish the value of chemoimmunotherapy for melanoma.  (+info)

Msh2 status modulates both apoptosis and mutation frequency in the murine small intestine. (5/1313)

Deficiency in genes involved in DNA mismatch repair increases susceptibility to cancer, particularly of the colorectal epithelium. Using Msh2 null mice, we demonstrate that this genetic defect renders normal intestinal epithelial cells susceptible to mutation in vivo at the Dlb-1 locus. Compared with wild-type mice, Msh2-deficient animals had higher basal levels of mutation and were more sensitive to the mutagenic effects of temozolomide. Experiments using Msh2-deficient cells in vitro suggest that an element of this effect is attributable to increased clonogenicity. Indeed, we show that Msh2 plays a role in the in vivo initiation of apoptosis after treatment with temozolomide, N-methyl-N'-nitro-N-nitrosoguanidine, and cisplatin. This was not influenced by the in vivo depletion of O6-alkylguanine-DNA-alkyltransferase after administration of O6-benzylguanine. By analyzing mice mutant for both Msh2 and p53, we found that the Msh2-dependent apoptotic response was primarily mediated through a p53-dependent pathway. Msh2 also was required to signal delayed p53-independent death. Taken together, these studies characterize an in vivo Msh2-dependent apoptotic response to methylating agents and raise the possibility that Msh2 deficiency may predispose to malignancy not only through failed repair of mismatch DNA lesions but also through the failure to engage apoptosis.  (+info)

Treatment of neoplastic meningitis with intrathecal temozolomide. (6/1313)

Neoplastic meningitis (NM) results from leptomeningeal dissemination of cancers arising within the central nervous system or metastasizing to the leptomeninges from systemic neoplasms. The inability to produce therapeutic drug levels intrathecally (i.t.) with systemic administration and the minimal efficacy of chemotherapeutic agents currently available for direct i.t. use limit therapy. Temozolomide [8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4([3H])-one] is a novel methylating agent with proven activity against intraparenchymal malignant gliomas (MGs). Insolubility of the standard formulation prevents its efficacious use as an i.t. agent, however. To overcome this obstacle, we have developed a unique microcrystalline formulation of temozolomide with greatly enhanced solubility. Treatment of athymic rats bearing subarachnoid MER- human MG xenografts with four doses of i.t. microcrystalline temozolomide over a 2-week period produced a 142% increase in median survival at individual doses of 2.2 micromol (P = 0.0073) and a >367% increase in median survival at individual doses of 6.8 micromol (P = 0.0015). At the higher dose tested, three of eight rats treated developed no neurological symptoms and had no evidence of residual tumor on histological examination after treatment. Use of this microcrystalline formulation in athymic rats bearing subarachnoid MER+ human MG xenografts increased median survival >132% (P < 0.0058) at both dose levels tested. Toxicity directly attributable to the i.t. administration of microcrystalline temozolomide was exhibited in the highest dose groups only and was limited to small patchy areas of focal demyelination involving <5% of spinal cord long tracks.  (+info)

DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents. (7/1313)

We have generated mice deficient in O6-methylguanine DNA methyltransferase activity encoded by the murine Mgmt gene using homologous recombination to delete the region encoding the Mgmt active site cysteine. Tissues from Mgmt null mice displayed very low O6-methylguanine DNA methyltransferase activity, suggesting that Mgmt constitutes the major, if not the only, O6-methylguanine DNA methyltransferase. Primary mouse embryo fibroblasts and bone marrow cells from Mgmt -/- mice were significantly more sensitive to the toxic effects of the chemotherapeutic alkylating agents 1,3-bis(2-chloroethyl)-1-nitrosourea, streptozotocin and temozolomide than those from Mgmt wild-type mice. As expected, Mgmt-deficient fibroblasts and bone marrow cells were not sensitive to UV light or to the crosslinking agent mitomycin C. In addition, the 50% lethal doses for Mgmt -/- mice were 2- to 10-fold lower than those for Mgmt +/+ mice for 1,3-bis(2chloroethyl)-1-nitrosourea, N-methyl-N-nitrosourea and streptozotocin; similar 50% lethal doses were observed for mitomycin C. Necropsies of both wild-type and Mgmt -/mice following drug treatment revealed histological evidence of significant ablation of hematopoietic tissues, but such ablation occurred at much lower doses for the Mgmt -/- mice. These results demonstrate the critical importance of O6-methylguanine DNA methyltransferase in protecting cells and animals against the toxic effects of alkylating agents used for cancer chemotherapy.  (+info)

A Phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignancies. (8/1313)

Temozolomide (TMZ) is an oral imidazotetrazinone that is spontaneously converted to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) at physiological pH. MTIC methylates DNA at the O6 position of guanine, although this lesion may be repaired by the enzyme O6-alkylguanine-DNA alkyltransferase (AGAT). In this study, TMZ was combined with cisplatin (CDDP), because both agents have single-agent activity against melanoma and other tumor types. Additionally, CDDP has been shown to inactivate AGAT, and subtherapeutic concentrations of CDDP have been shown to increase the sensitivity of leukemic blasts to TMZ. This Phase I study sought to determine the toxicities, recommended dose, and pharmacological profile of the TMZ/CDDP combination. Patients were treated with oral TMZ daily for 5 consecutive days together with CDDP on day 1 (4 h after TMZ) every 4 weeks at the following TMZ (mg/m2/day)/CDDP (mg/m2) dose levels: 100/75, 150/75, 200/75, and 200/100. Plasma samples were obtained on days 1 and 2 to evaluate the pharmacokinetic parameters of TMZ alone and in combination with CDDP. Fifteen patients received a total of 44 courses of TMZ/CDDP. The principal toxicities of the regimen consisted of neutropenia, thrombocytopenia, nausea, and vomiting, which were intolerable in two of six new patients treated at the 200/100 mg/m2 dose level. Of five patients receiving 17 courses at the next lower dose level (200/75 mg/m2), none experienced dose-limiting toxicity. Antitumor activity was observed in patients with non-small cell lung cancer, squamous cell carcinoma of the tongue, and leiomyosarcoma of the uterus. Pharmacokinetic studies of TMZ revealed the following pertinent parameters (mean +/- SD): time to maximum plasma concentration (Tmax) = 1.1+/-0.6 h (day 1) and 1.7+/-0.9 h (day 2); elimination half-life (t1/2) = 1.74+/-0.22 h (day 1) and 2.35+/-0.70 h (day 2); and clearance (Cl(s)/F) = 115+/-27 ml/min/m2 (day 1) and 141+/-109 ml/min/m2 (day 2). TMZ drug exposure, described by the area under the plasma concentration-time curve (AUCinfinity) and the maximum plasma concentration (Cmax), was similar on days 1 and 2. On the basis of these results, the recommended doses for Phase II clinical trials are TMZ 200 mg/m2/day for 5 days with 75 mg/m2 CDDP on day 1, every 4 weeks. The addition of CDDP did not affect the tolerable dose of single-agent TMZ (200 mg/m2/day x 5 days), nor did it substantially alter the pharmacokinetic behavior of TMZ.  (+info)

TY - JOUR. T1 - Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age. AU - Winship, Amy L.. AU - Bakai, Monika. AU - Sarma, Urooza. AU - Liew, Seng H.. AU - Hutt, Karla J.. PY - 2018/4/25. Y1 - 2018/4/25. N2 - Dacarbazine is commonly administered for the treatment of cancers prevalent in reproductive age females. However, investigations of off-target effects of dacarbazine on the ovary are limited. We assessed the impact of dacarbazine on the ovarian reserve of primordial follicles, essential for fertility. Eight week and 6 month old C57BL/6 J mice were administered with dacarbazine or saline on day (d)0 and d7, then sacrificed after 12 hours (h), or 14d (n = 4-5/group). Follicle numbers, follicle density, serum AMH and corpora lutea were quantified and estrous cyclicity monitored. In reproductively young mice, dacarbazine did not affect primordial follicle numbers at 12 h, but resulted in a 36% reduction at 14d (p , 0.05). Dacarbazine-mediated primordial follicle ...
TY - JOUR. T1 - Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells. AU - Lee, Eun Sang. AU - Ko, Kyung Kon. AU - Joe, Young Ae. AU - Kang, Seok Gu. AU - Hong, Yong Kil. PY - 2011/1/1. Y1 - 2011/1/1. N2 - The alkylating agent temozolomide (TMZ) is an effective drug used for the treatment of malignant gliomas. However, tumor relapse combined with the development of drug resistance remains a significant problem. To clarify the mechanism of the resistance of glioma cells to TMZ chemotherapy, TMZ-resistant glioma cell lines (TR cells) were generated using U373 and U251 human glioma cells, and TMZ-resistance was confirmed via viability and apoptosis assays. The TMZ-resistance of TR cells was not associated with the TMZ-resistance molecule O6-methylguanine-DNA-methyltransferase. Notably, the expression level of signal transducers and activators of transcription 3 (STAT3) and serine 727-phosphorylated STAT3 (pSTAT3-Ser727) was highly increased in TR cells, ...
All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.. Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.. After completion of combined modality therapy, patients will have 4 weeks without any therapy.. Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be ...
Tumor recurrence after initial treatment with radiation and temozolomide is the major cause of mortality for patients with glioblastomas, yet recurrences are understudied because of the dearth of matched tumors samples. This is of particular concern because temozolomide treatment profoundly affects the tumors evolution as evidenced by dramatic alterations in the genomic landscape of recurrent tumors compared with their primary tumor counterparts (65). A big effort has been made recently to understand this evolutionary process by comparing the genomic and proteomic profiles of primary versus recurrent tumors and correlating these datasets with treatment regimens, radiologic data, and clinical history (65-67). However, in these studies, no functional assays were carried out to understand mechanisms of temozolomide resistance due to the lack of matching primary and recurrent cell lines. We developed an in vivo model of tumor recurrence in mice that allows us to understand temozolomide resistance ...
Tumor recurrence after initial treatment with radiation and temozolomide is the major cause of mortality for patients with glioblastomas, yet recurrences are understudied because of the dearth of matched tumors samples. This is of particular concern because temozolomide treatment profoundly affects the tumors evolution as evidenced by dramatic alterations in the genomic landscape of recurrent tumors compared with their primary tumor counterparts (65). A big effort has been made recently to understand this evolutionary process by comparing the genomic and proteomic profiles of primary versus recurrent tumors and correlating these datasets with treatment regimens, radiologic data, and clinical history (65-67). However, in these studies, no functional assays were carried out to understand mechanisms of temozolomide resistance due to the lack of matching primary and recurrent cell lines. We developed an in vivo model of tumor recurrence in mice that allows us to understand temozolomide resistance ...
TY - JOUR. T1 - Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate dehydrogenase concentration in the testis. AU - Kumar, S. Ganesh. AU - Narayana, K.. AU - Bairy, K. L.. AU - DSouza, Urban J.A.. AU - Samuel, Vijaya Paul. AU - Gopalakrishna, K.. PY - 2006/9/5. Y1 - 2006/9/5. N2 - Treatment of cancers with cytotoxic agents such as alkylating drugs often, but not always results in transient to permanent testicular dysfunction. The present study was planned to investigate the effects of dacarbazine [5-(3,3-dimethyltriazeno) imidazole-4-carboxamide] on testicular function in mice. Swiss albino mice (9-12 weeks old) were treated with 0, 5, 25, 50, or 100 mg/kg body weight/day dacarbazine (i.p.) for 5 days at intervals of 24 h between treatments. Mice were sacrificed on days 7, 14, 21, 28, 35, 49, and 70 after the last treatment (6 mice/dose/sample time), and the epididymal sperm count, sperm motility, sperm morphology, ...
Dose limiting toxicity will be assessed during the dose-escalation part of Phase IIa from day 1 through day 21 of the first cycle.. Response will be measured using RECIST criteria every 6 weeks (after every 2 cycles of treatment). Patients with stable or responding disease at each assessment may receive additional treatment for a maximum of 6 cycles of induction. Patients with stable or responding disease after induction may receive L19IL2 (without dacarbazine) every 2 weeks as maintenance therapy.. Tumor expression of ED-B FN and tumor uptake of L19IL2 and of Dacarbazine will be assessed via immunohistochemistry and/or other methods deemed appropriate on tumor tissue biopsies. Tumor biopsy will be performed on superficial accessible cutaneous and/or subcutaneous lesions only. Tumor biopsy will be considered optional and will not preclude patient entry on to study should the patient refuse.. Pharmacokinetics of L19IL2, Dacarbazine and AIC will be assessed from serial blood samples using standard ...
There is increasing experimental evidence to suggest that expression of O6-alkylguanine-DNA-alkyltransferase (ATase) is a major factor in resistance to dacarbazine (DTIC). We recently demonstrated a progressive ATase depletion in human peripheral lymphocytes with nadir levels occurring at 4-6 h after DTIC administration (Lee et al., 1991). Therefore in an attempt to improve the clinical response rate of DTIC, fotemustine was administered 4 h after DTIC administration; since in the case of fotemustine, ATase removes the chloroethyl lesions from the O6-position of guanine, thereby preventing the formation of the cytotoxic cross-links. Sixty patients with widely metastatic melanoma received DTIC at 400, 500 or 800 mg m-2 followed by fotemustine (100 mg m-1) at 4 h after DTIC administration. Treatment was repeated every 28 days with a total of 169 cycles of chemotherapy administered; 75, 57 and 37 treatment cycles with 400, 500 and 800 mg m-2 DTIC groups respectively. Eighteen of the 60 patients ...
TY - JOUR. T1 - A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma. AU - Hersh, Evan M.. AU - ODay, Steven J.. AU - Powderly, John. AU - Khan, Khuda D.. AU - Pavlick, Anna C.. AU - Cranmer, Lee D.. AU - Samlowski, Wolfram E.. AU - Nichol, Geoffrey M.. AU - Yellin, Michael J.. AU - Weber, Jeffrey S.. PY - 2011/6/1. Y1 - 2011/6/1. N2 - Objective: Ipilimumab is a fully human, anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody that has demonstrated antitumor activity in advanced melanoma. We evaluated the safety and efficacy of ipilimumab alone and in combination with dacarbazine (DTIC) in patients with unresectable, metastatic melanoma. Methods: Chemotherapy-naïve patients were randomized in this multicenter, phase II study to receive ipilimumab at 3 mg/kg every 4 weeks for four doses either alone or with up to six 5-day courses of DTIC at 250 mg/m2/day. The primary efficacy endpoint was objective response ...
Many chemotherapeutic agents have been associated with pulmonary toxicities. Busulfan was the first chemotherapeutic drug with evidence of drug-induced lung disease 6. Other alkylating agents, such as cyclophophamide and chlorambucil have been clearly associated with pulmonary toxicity as well 7. Dacarbazine, which is closely related to temozolomide has been associated with pulmonary adverse effects only when used in combination with fotemustine, a nitrosourea agent 8.. Temozolomide is an imidazotetrazine compound and a derivative of the alkylating agent dacarbazine (second-generation oral alkylating agent). Temozolomide has proven activity against recurrent glioma 9. In a recent randomised trial, concomitant and adjuvant temozolomide chemotherapy with radiation significantly improved progression free survival and overall survival in glioblastoma multiforme patients 2.. Various adverse reactions have been reported, but they are usually mild to moderate and in the majority of cases do not require ...
Brentuximab Vedotin Plus Dacarbazine or Bendamustine: New Options for Older Patients with Hodgkin Lymphoma? - Meeting News, Special Edition - ASH Clinical News
A French team of investigators evaluated whether irinotecan and bevacizumab added to temozolomide-based chemoradiation would improve the prognosis of patients with unresectable glioblastoma. The study results show a trend towards improved progression-free survival and are presented by Dr B. Chauffert at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.. This phase II, randomized trial enrolled 120 patients, aged 18 to 70 years with de novo unresectable glioblastoma, Karnofsky performance status , 50 and recursive partitioning analysis (RPA) class 5. Patients were randomized, 60 patients per arm, to receive four cycles of neo-adjuvant bevacizumab plus irinotecan prior to radiotherapy with concurrent temozolomide and bevacizumab or to receive control treatment of concomitant temozolomide plus radiotherapy for 6 months.. Clinical factors were well balanced between arms and cross-over was allowed upon progression. An evaluation done at 16 months after the treatment ...
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Background: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remain to be elucidated. Methods: To elucidate the mechanism maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). LncRNAs from four public datasets were reanalyzed, and the candidate lncRNA ADAMTS9-AS2 was evaluated in TMZ-treated GBM patients and in vitro cell lines. Results: Reanalysis of lncRNA expression profiles identified ADAMTS9-AS2 as significantly overexpressed in TMZ-resistant GBM cells and as positively associated with the IC50 of TMZ in GBM cells. Overexpression of ADAMTS9-AS2 was also significantly associated with poor TMZ response and shorter progression-free survival (PFS) in TMZ-treated GBM patients. Knockdown of ADAMTS9-AS2 inhibited proliferation and attenuated the IC50 of TMZ, as well as mitigating invasion and migration in TMZ-resistant GBM cells. ...
Background: Temozolomide (TMZ) is the most widely used drug to treat glioblastoma (GBM), which is the most common and aggressive primary tumor of the Central Nervous System and one of the hardest challenges in oncotherapy. TMZ is an alkylating agent that induces autophagy, apoptosis and senescence in GBM cells. However, therapy with TMZ increases survival after diagnosis only from 12 to 14.4 months, making the development of combined therapies to treat GBM fundamental. One candidate for GBM therapy is Resveratrol (Rsv), which has additive toxicity with TMZ in several glioma cells in vitro and in vivo. However, the mechanism of Rsv and TMZ additive toxicity, which is the aim of the present work, is not clear, especially concerning cell cycle dynamics and long term effects. Methods: Glioma cell lines were treated with Rsv and TMZ, alone or in combinations, and the induction and the role of autophagy, apoptosis, cell cycle dynamics, protein expression and phosphorylation status were measured. We ...
Clinical trial for Brain and Central Nervous System Tumors , Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
A Randomized, Placebo Controlled Phase IIb/III Study of ABT-414 with Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects with Newly Diagnosed Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance 1)
By sacrificing its only alkyl component to the TMZ-induced lethal depletion of alkyl products on tumoural DNA, MGMT serves as a suicidal DNA repair enzyme. Theoretically, this irreversible depletion of the MGMT protein could be exploited by increasing tumoural exposure to TMZ. The effect might be even more prominent when MGMT promoter is hypermethylated, although the impact of MGMT promoter methylation could not be demonstrated in the present study. Nonetheless this mechanism also accounts for myelosuppression, the main concern of long-term use of TMZ, since MGMT protein in normal cells can also be depleted by TMZ. It is more common in haematopoietic stem cells contributing to toxicity for patients using this alkylating agent.3 In a cohort that comprised 114 patients, 39 (34%) were observed to have CTCAE grade 3 haematological toxicity during administration of TMZ. The study included all patients who received 1 to 57 cycles of TMZ.8 The French SV3 Study also evaluated the effect of prolonged TMZ ...
Clinical trial for Malignant neoplasm of brain , An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo for Newly Diagnosed Patients With Glioblastoma (GBM a Malignant Brain Cancer)
Rare Cancer News & Clinical Trials » Trial - CNS Tumor » An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo, for Newly Diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer ...
Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a tumor angiogenesis marker, and of human interleukin-2 (IL2). L19-IL2 delivers IL2 to the tumor site exploiting the selective expression of EDB on newly formed blood vessels. Previously, the recommended dose of L19-IL2 monotherapy was defined as 22.5 million international units (Mio IU) IL2 equivalents. In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma.. Experimental Design: The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m2 of dacarbazine on day 1 of a 3-weekly therapy cycle. Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. Up to six treatment cycles were given, followed by a maintenance regimen with biweekly L19-IL2.. Results: The recommended dose of L19-IL2 in combination with dacarbazine was defined ...
Fingerprint Dive into the research topics of Augmented HR repair mediates acquired temozolomide resistance in glioblastoma. Together they form a unique fingerprint. ...
UP TO 50 PERCENT OF BRAIN TUMORS RESISTANT TO STANDARD CHEMOTHERAPEUTIC AGENT TMZ When a patient presents with a malignant glioblastoma, the current standard therapy is total resection surgery followed by radiation, either alone or in combination with temozolomide (TMZ) chemotherapy.1 Used to treat several types of cancer, orally-administered alkylating agent TMZ is known to…
Temozolomide is used in the treatment of brain tumor.get complete information about temozolomide including usage, side effects, drug interaction, expert advice along with medicines associated with temozolomide at 1mg.com
New Zealand has the second highest incidence of melanoma skin cancer in the world. Chemotherapy is the standard treatment for melanoma derived tumours which have undergone metastasis and current therapies have limited benefit. There is a great need for new therapies and to increase the efficacy of current therapies. Temozolomide (TMZ) is a chemotherapy agent effective in the treatment of both metastatic melanoma and glioblastoma (brain cancer), although TMZ resistance has been observed in many tumours. The activity of the DNA repair enzyme O6 methyl-guanine methyltransferase (MGMT) is thought to be largely responsible for TMZ resistance. MGMT protects the cell from the effects of TMZ by removing cytotoxic lesions placed on the DNA. Mechanisms of regulation of MGMT expression remain unclear in melanoma. DNA methylation at the MGMT promoter has been linked to MGMT silencing in some cancers and has been associated with specific chromatin modifications. The present study was aimed at investigating ...
Phase II: Primary Objectives: -To determine the effectiveness of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ)
Dacarbazine (or DTIC), is a chemotherapy drug used to treat Hodgkin lymphoma, melanoma and soft tissue sarcoma. It may also be used to treat other cancers.
In this clinical trials, was shown that patients who were receiving vemurafenib had a reduction of 74% in the risk for progression of the disease or death, compared with patients who were receiving dacarbazine chemotherapy. Mean progression-free survival was 5.3 months in the vemurafenib group, compared with 1.6 months in the dacarbazine group. At 6 months, estimated survival was 84% in the patients who were treated with vemurafenib and 64% in the patients who were treated with dacarbazine. In this study, which was conducted at 104 centers in 12 countries, patients who participated had advance forms of melanoma, who were previously untreated or with inoperable stage III or IV metastatic melanoma and a V600E mutation in the BRAF gene. Patients receive either vemurafenib, 960 mg, orally, twice a day or dacarbazine 1000 mg/m2 of body-surface area, in intravenously infusion, every 3 weeks. Common adverse effects which were associated with vemurafenib were arthralgia, rash, fatigue, alopecia, ...
Current therapy for metastatic melanoma remains highly unsatisfactory (1, 11, 12). Most chemotherapy regimens contain the alkylating agent dacarbazine. This drug and its congener, temozolomide, produce objective response rates in patients with melanoma in 10% to 20% of patients. It is currently not known if dacarbazine prolongs survival in patients with melanoma. Combination chemotherapy in the form of the Dartmouth regimen has higher reported response rates, but in a prospective randomized trial showed no advantage in survival over dacarbazine alone (13). More recently, IFN-α and interleukin-2 have been incorporated into biochemotherapy regimens that also showed very high response rates (45-60%) in single-institution phase II trials. However, in a prospective randomized clinical trial, biochemotherapy failed to show any survival benefit over chemotherapy alone (4). Therefore, it seems that varying combinations of currently used drugs will have only limited utility in this disease.. The ...
Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, DAmato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 08 01; 125(15):2610-2620 ...
As this eMedTV article discusses, dacarbazine may cause nausea, diarrhea, and other side effects. This resource describes other possible reactions and explains which problems require urgent medical attention.
George Demetri, MD, professor of medicine, Harvard Medical School, director of the Sarcoma Center, Dana Farber Brigham Womens Cancer Center, on the mutagenic properties of dacarbazine.
This eMedTV Web page focuses on dosing guidelines for dacarbazine, including how the amount is calculated, how often it is given, and how long treatment will last. This article also offers details on what to expect during treatment with this drug.
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In glioblastoma, the benefit from temozolomide chemotherapy is largely limited to a subgroup of patients (30-35%) with tumors exhibiting methylation of the promoter region of the O-methylguanine-DNA methyltransferase (MGMT) gene. In order to allow more patients to benefit from this treatment, we explored magnetic resonance image-guided microbubble-enhanced low-intensity pulsed focused ultrasound (LIFU) to transiently open the blood-brain barrier and deliver a first-in-class liposome-loaded small molecule MGMT inactivator in mice bearing temozolomide-resistant gliomas. We demonstrate that a liposomal O-(4-bromothenyl)guanine (OBTG) derivative can efficiently target MGMT, thereby sensitizing murine and human glioma cells to temozolomide in vitro. Furthermore, we report that image-guided LIFU mediates the delivery of the stable liposomal MGMT inactivator in the tumor region resulting in potent MGMT depletion in vivo. Treatment with this new liposomal MGMT inactivator facilitated by LIFU-mediated ...
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As reported in this issue of The ASCO Post, Robert and colleagues recently published a phase III study comparing the anti-programmed death 1 (PD-1) antibody nivolumab with the standard melanoma chemotherapy dacarbazine in the front-line treatment of patients with advanced BRAF wild-type melanoma.1 In this study, nivolumab was shown to be superior to dacarbazine in improving overall survival, progression-free survival, and objective response rate. Nivolumab was also associated with a lower rate of high-grade side effects than dacarbazine. Of importance, this study is the first to demonstrate that nivolumab, and any anti-PD-1 antibody, improves overall survival compared with a standard comparator in a large, well-conducted, randomized, placebo-controlled phase III study.. The high response rate and favorable toxicity profile of nivolumab and pembrolizumab (Keytruda), another anti-PD-1 antibody, in patients with melanoma have been well known from large, previously published, early-phase studies.2-5 ...
The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma (HL). The approval was based on the phase 3 ECHELON-1 trial. Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine. In this trial, researchers compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy. According to an independent review committee, A+AVD provided a significant improvement in modified PFS compared to ABVD. ...
DACLIZUMAb, Dacarbazine, DACARBAZINE, Dabrafenib, Dabigatran, D4T, Online Electronic Medical Diagnosis and Drugs, Medications, Articles, Glossary
A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase 1 of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting ...
Tumor microenvironments can promote stem cell maintenance, tumor growth, and therapeutic resistance, findings linked by the tumor-initiating cell hypothesis. Standard of care for glioblastoma (GBM) includes temozolomide chemotherapy, which is not curative, due, in part, to residual therapy-resistant brain tumor-initiating cells (BTICs). Temozolomide efficacy may be increased by targeting carbonic anhydrase 9 (CA9), a hypoxia-responsive gene important for maintaining the altered pH gradient of tumor cells. Using patient-derived GBM xenograft cells, we explored whether CA9 and CA12 inhibitor SLC-0111 could decrease GBM growth in combination with temozolomide or influence percentages of BTICs after chemotherapy. In multiple GBMs, SLC-0111 used concurrently with temozolomide reduced cell growth and induced cell cycle arrest via DNA damage in vitro. In addition, this treatment shifted tumor metabolism to a suppressed bioenergetic state in vivo. SLC-0111 also inhibited the enrichment of BTICs after ...
TY - JOUR. T1 - A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer. AU - Pishvaian, Michael J.. AU - Slack, Rebecca S.. AU - Jiang, Wei. AU - He, A. Ruth. AU - Hwang, Jimmy J.. AU - Hankin, Amy. AU - Dorsch-Vogel, Karen. AU - Kukadiya, Divyesh. AU - Weiner, Louis M.. AU - Marshall, John L.. AU - Brody, Jonathan R.. N1 - Funding Information: This work was funded by the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancers at the Lombardi Comprehensive Cancer Center. AbbVie, Inc, provided the veliparib and temozolomide as well as partial research funding for the correlative science. Michael J. Pishvaian and Jonathan R. Brody are supported by the National Cancer Institute of the National Institutes of Health (1R01CA212600-01) and by a 2015 Pancreatic Cancer Action Network-American Association for Cancer Research Acceleration Network grant (15-90-25-BROD). Publisher Copyright: © 2018 American Cancer Society ...
In this case report we describe the management of a highly invasive multi-centric GBM in an older patient following partial tumor resection and treatment with a combination of standard therapy, fasting, and a R-KD. The patients response to this therapeutic approach was unusual, as no prior reports have appeared to our knowledge describing regression of GBM within 2.5 months from the time of diagnosis in either younger (, 50 yrs) or older (, 50 yrs) patients using standard radiation and temozolomide therapy alone. Although the patient in this study expressed hypermethylation of the MGMT gene promoter, which enhances the therapeutic action of temozolomide and is prognostic for increased survival [26], no prior cases of rapid GBM regression have been reported in patients with the MGMT hypermethylation phenotype to our knowledge. Temozolomide is an oral alkylating agent that damages DNA and is used as first and second line GBM treatment [2, 26, 29]. Continuous temozolomide administration depletes ...
Glioblastoma is the most malignant brain tumor without efficiently therapeutic strategy. Improvement of patient prognosis by the combined therapy of radiation with temozolomide (TMZ) is restricted within a small window due to the higher prevalence of recurrence. In particular, O6-methylguanine-DNA methyltransferase (MGMT)-mediated DNA repair is well defined as a characteristic of TMZ resistance, but MGMT-negative glioblastoma still develops an unknown mechanism to counteract TMZ-induced apoptosis. Therefore, the mechanisms underlying the resistance of glioblastoma in response to TMZ-mediated chemotherapy remains controversial. Previously, we clarified that aberrantly activated cytochrome P450 17A1-mediated neurosteroidogenesis caused TMZ resistance in MGMT-deficient glioblastoma through increasing the secretion of dehydroepiandrosterone (DHEA), which maintains the health of neurons and astrocytes in addition to being an adrenal gland-secreted steroid hormone. However, how DHEA alters the ...
Clinically achievable concentrations of temozolomide (TMZ) produce cytotoxic effects only in mismatch repair (MMR)-proficient cells endowed with low O6-methylguanine-DNA methyltransferase (MGMT) activity. Aim of the present study was to investigate the molecular mechanisms underlying acquired resistance of melanoma cells to TMZ and the effect of O6-benzylguanine (BG), a specific MGMT inhibitor, on the development of a TMZ-resistant phenotype. Three MMR-proficient melanoma cell clones with low or no MGMT activity were treated daily for 5 days with 50 µmol/l TMZ, alone or in combination with 5 µmol/l BG. Parental clones and sublines established after one or four cycles of treatment were analyzed for sensitivity to TMZ or TMZ+BG and for other parameters. The sublines established after one cycle of TMZ or TMZ+BG exhibited a marked increase in MGMT activity and resistance to TMZ alone. BG only partially reversed acquired resistance to the drug. In some cases, alterations in the MMR system accounted ...
Geneva, Switzerland - March 10, 2008 - Anavex Life Sciences Corp. (ANAVEX) (OTCBB: AVXL) today announced that ANAVEX 7-1037 has demonstrated its ability to significantly delay the growth of cancerous tumors in patient-derived xenografts during advanced pre-clinical studies. The human tumor xenografts were developed in ANAVEX labs using a sample taken from a person suffering from clear cell sarcoma. Clear cell sarcoma is a rare type of melanoma (skin cancer) that is difficult to treat.. In comparative pre-clinical studies, ANAVEX 7-1037 reduced tumor growth by 69% with minimal side effects. Significantly, Dacarbazine, a currently available chemotherapy drug used to treat melanoma and other types of cancer, was found to be completely inactive in the same tests. ANAVEX 7-1037 is the companys lead drug candidate for the treatment of a number of cancers, including that of the breast, colon, prostate and melanoma. It exhibits a high safety profile and disease-modifying potential.. These results ...
Inhibitory Effects and Mechanism analysis on the Inhibition of Dacarbazine on Melanoma Stem Cells Proliferation in vitro Abstract Melanoma is a growing interest over the past decades and a very diffi
This trial is the first to study Optune in combination with an investigational drug ST. HELIER, Jersey-(BUSINESS WIRE)- Novocure (NASDAQ:NVCR) announced today a new arm for a phase 1b study to evaluate the safety of marizomib and temozolomide in combination with Optune, Novocures Tumor Treating Fields (TTFields) delivery system, as adjuvant treatment for patients with newly diagnosed glioblastoma (GBM) following radiation therapy with concurrent temozolomide. The trial is the first to study Optune in combination with an investigational drug. Marizomib is a novel, brain-penetrant proteasome inhibitor developed by Triphase Accelerator Corporation and acquired by Celgene Corporation. Celgene is responsible for marizomibs development. This collaboration marks an important first step toward testing Optune with a promising new investigational compound for the treatment of GBM, said Principal Investigator Dr. Roger Stupp, Associate Director for Strategic Initiatives at the Robert H. Lurie ...
The anti-inflammatory ibudilast shows early preclinical promise against glioblastoma cell lines when combined with temozolomide, according to new research.
3798 Background: Malignant gliomas are highly lethal tumors that display resistance to current therapies. The best treatment modality currently available for these tumors is a combination of maximal surgical resection followed by radiation therapy and concurrent temozolomide, an oral alkylating imidazotetrazine derivative. Although this combination has demonstrated activity, development of resistance and disease progression is common. Thus, additional agents to augment the effectiveness of this approach are needed. The presence of increased Ras signaling in malignant glioma offers a potential novel target. We now report the in vitro and orthotopic in vivo results of combination therapy using irradiation, temozolomide and SCH66336, an oral farnesyl transferase inhibitors, in a murine model of glioblastoma multiforme (GBM). Methods: To examine the activity of radiation, temozolomide, and SCH66336 U87 in vitro and in U87-induced intracranial tumors in SCID or nude mice were evaluated following ...
Glioblastoma multiforme (GMB) is the most malignant and common type of all astrocytic tumors. Current standard of care entails maximum surgical resection of the tumor, followed by radiotherapy and chemotherapy, usually by the alkylating agent Temozolomide (TMZ). Despite this aggressive combination t …
Carter, S K. and Friedman, M A., 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (dtic, Dic, nsc- -45388)-a new antitumor agent with activity against malignant melanoma. (1972). Subject Strain Bibliography 1972. 568 ...
Temozolomide (TMZ) is standard chemotherapy for glioblastoma multiforme (GBM). Intratumoral hypoxia is common in GBM and may be associated with the development of TMZ resistance. Oxygen therapy has previously been reported to potentiate the effect of
TY - JOUR. T1 - Clinical trials of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) given intravenously in the treatment of malignant melanoma in Uganda.. AU - Vogel, C. L.. AU - Comis, R.. AU - Ziegler, J. L.. AU - Kiryabwire, J. W.. PY - 1971/4/1. Y1 - 1971/4/1. UR - http://www.scopus.com/inward/record.url?scp=0015039859&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0015039859&partnerID=8YFLogxK. M3 - Article. C2 - 5118684. AN - SCOPUS:0015039859. VL - 55. SP - 143. EP - 149. JO - Journal of the National Cancer Institute. JF - Journal of the National Cancer Institute. SN - 0027-8874. IS - 2. ER - ...
BackgroundThis multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.MethodsPatients received temozolomide 100-125 mg/m2/day (days 1-5) and irinotecan 10 mg/m2/day (days 1-5 and 8-12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.ResultsSixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6% (95% confidence interval [CI], 19.5%-48.0%). Median duration of response was 27.0 weeks ...
The discovery that BRAF is a driver oncogene in cancer, and complementary improvements in our understanding of the immune system have resulted in fresh targeted and immune\therapies for metastatic melanoma. lessons from this paradigm shift in treatment and the opportunities for further improvements in results for melanoma individuals. selected tumor immunotherapy as the 2013 breakthrough of the year (Couzin\Frankel, 2013). 2.?Pre\2011 therapies The development of effective treatments for advanced melanoma has been a long hard road. In 1975 the FDA authorized the alkylating agent dacarbazine (5\[3,3\dimethyl\1\triazenyl]\imidazole\4\carboxamide; DTIC) for advanced metastatic melanoma (Number?1), although objective clinical reactions (mostly partial reactions) were seen only in 13C20% of individuals and durable reactions were extremely rare (Eggermont and Kirkwood, 2004). Temozolomide, an orally available DTIC analogue, did little to improve these reactions (Middleton et?al., 2000) and for the ...
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to st
At a median follow-up of 3.6 years, 128 deaths had occurred. As of October 2014, 68 patients were alive (median follow-up of 9.1 years). There was no difference in overall survival between the 2 treatment arms: 3.9 years with temozolomide and 3.8 years with nitrosourea. No difference in progression-free survival was observed between treatment arms. A trend was found toward improved survival in patients with a mutated IDH1 gene treated with radiation plus temozolomide versus radiation plus nitrosourea ...
Background: Oncogenic mutations in BRAF occur in 8% of patients with advanced colorectal cancer (CRC) and have been shown to correlate with poor prognosis. In contrast to BRAF mutant (MT) melanoma, where the BRAF inhibitor PLX4032 has shown significant increases in response rates and overall survival compared to standard Dacarbazine treatment, only minor responses to PLX4032 treatment have been reported in BRAFMT CRC. Clear understanding of the vulnerabilities of BRAFMT CRC is important, and identification of druggable targets uniquely required by BRAFMT CRC tumors has the potential to fill a gap in the therapeutic armamentarium of advanced CRC. The aim of this study was to identify novel resistance mechanisms to MAPK inhibition in BRAFMT CRC.. Methods: Paired BRAFMT/WT RKO and VACO432 CRC cell line models and non-isogenic BRAFMT LIM2405, WiDR and COLO205 CRC cells were used. Changes in protein expression/activity were assessed by Western Blotting. Interaction between MEK1/2 and JAK1/2 ...
Fig. S3 (a, c) Melanoma cells were treated with 1 μg/ml cisplatin or 250 μg/ml dacarbazine and harvested at various time-points. And the menin expression was determined with Western blotting. (b, d) Melanoma cells were treated with the indicated concentrations of cisplatin or dacarbazine, and the menin expression was detected by Western blotting. (e) A375 cells were treated for 24 hrs with various doses of Cisplatin and then analysed for apoptosis via Annexin V-PI staining. (f) menin, γ-H2A.X, cyclinB1 and cyclinB2 protein level were detected by Western blot. ...
Background: TTFields is an established antimitotic treatment modality delivered to patients by a portable, home use, medical device. Here we evaluate whether this antimitotic effect can be translated into improved survival in a clinical setting. Based on a pre-specified interim analysis on 315 patients, the IDMC recommended early trial closure; we here report the first analysis of the full dataset of 700 randomized patients. Methods: This prospective phase 3 trial randomized patients with newly diagnosed glioblastoma, after completion of concomitant chemoradiotherapy, to receive either adjuvant temozolomide (TMZ) chemotherapy alone, or TMZ with TTFields (TTF/TMZ). The primary endpoint was progression-free survival, with overall survival, safety, cognitive function and quality of life as secondary endpoints. Results: (ITT) From 2009 to 2014, 700 Grade IV astrocytoma (glioblastoma) patients (68% male) were randomized 2:1. Patient characteristics were well balanced: median age was 56 and 57 years ...
Enter Tumor Treating Fields (TTF): a little bit science fiction, a little bit science fact. I have to admit I was very skeptical when I first heard of the technology, and was even less enthused when I saw what a nuisance it is for patients - but it works. In 2015, investigator Roger Stupp (who developed temozolomide treatment in the first place) showed that adding TTF to standard treatment improved median overall survival from 16.6 to 19.6 months, and improved a patients chances of surviving 2 years from 29% to 43%3 - thats as big a step forward as adding temozolomide was in 2005.. Whats the magic? TTF subjects tumor cells to rapidly alternating electrical fields, disrupting cell division. And since its uncontrolled cell division that makes a cell cancerous in the first place, the TTF approach hits the cancer right where it hurts.. TTF doesnt cause nausea, or fatigue, or infections, or low blood counts. It doesnt even require patients come into the office for treatment- but there is a down ...
This randomized phase II trial is studying the side effects and how well giving bevacizumab together with irinotecan or temozolomide works in treating p
Alfa Aesar™ 2-Bromo-1-(cyanomethyl)imidazole-4,5-dicarbonitrile, 97% 250mg Alfa Aesar™ 2-Bromo-1-(cyanomethyl)imidazole-4,5-dicarbonitrile, 97%...
Notes from the article: The addition of Zinc to Temozolomide (Temodar) stopped the growth of Glioblastoma cells that were previously Temodar resistant
Long-term data from the phase 3 EF-14 study showed that Optune plus temozolomide had a survival benefit compared to temozolomide alone.
RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma This study is ongoing, but not recruiting…
Characterization of glioblastoma (GB) response to treatment is a key factor for improving patients survival and prognosis. MRI and magnetic resonance spectroscopic imaging (MRSI) provide morphologic and metabolic profiles of GB but usually fail to produce unequivocal biomarkers of response. The purpose of this work is to provide proof of concept of the ability of a semi-supervised signal source extraction methodology to produce images with robust recognition of response to temozolomide (TMZ) in a preclinical GB model. A total of 38 female C57BL/6 mice were used in this study. The semi-supervised methodology extracted the required sources from a training set consisting of MRSI grids from eight GL261 GBs treated with TMZ, and six control untreated GBs. Three different sources (normal brain parenchyma, actively proliferating GB and GB responding to treatment) were extracted and used for calculating nosologic maps representing the spatial response to treatment. These results were validated with an
Characterization of glioblastoma (GB) response to treatment is a key factor for improving patients survival and prognosis. MRI and magnetic resonance spectroscopic imaging (MRSI) provide morphologic and metabolic profiles of GB but usually fail to produce unequivocal biomarkers of response. The purpose of this work is to provide proof of concept of the ability of a semi-supervised signal source extraction methodology to produce images with robust recognition of response to temozolomide (TMZ) in a preclinical GB model. A total of 38 female C57BL/6 mice were used in this study. The semi-supervised methodology extracted the required sources from a training set consisting of MRSI grids from eight GL261 GBs treated with TMZ, and six control untreated GBs. Three different sources (normal brain parenchyma, actively proliferating GB and GB responding to treatment) were extracted and used for calculating nosologic maps representing the spatial response to treatment. These results were validated with an
Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma This study is ongoing, but not recruiting participants….
The goal of this clinical research study is to learn if lapatinib when given in combination with temozolomide can help to control ependymoma that has come back after treatment. The safety of this combination will also be studied.
"Dacarbazine". The American Society of Health-System Pharmacists. Archived from the original on 11 September 2017. Retrieved 8 ...
Tetrazines include dacarbazine, mitozolomide and temozolomide. Aziridines include thiotepa, mytomycin and diaziquone (AZQ). ...
Chemotherapy drugs such as Dacarbazine have been the backbone of metastatic melanoma treatment since FDA approval in 1975 ... In June 2011, a clinical trial of ipilimumab plus dacarbazine combined this immune system booster with the standard ... June 2011). "Ipilimumab plus dacarbazine for previously untreated metastatic melanoma". The New England Journal of Medicine. ...
June 2011). "Ipilimumab plus dacarbazine for previously untreated metastatic melanoma". N. Engl. J. Med. 364 (26): 2517-26. doi ... In June 2011, a clinical trial of ipilimumab plus dacarbazine combined this immune system booster with the standard ... Chemotherapy drugs such as Dacarbazine have been the backbone of metastatic melanoma treatment since FDA approval in 1975 ...
Dacarbazine).aspx DeVita V, Simon R, Hubbard S, Young R, Berard C, Moxley J, Frei E, Carbone P, Canellos G (1980). "Curability ... dacarbazine regimen?". J Clin Oncol. 22 (8): 1532-3. doi:10.1200/JCO.2004.99.010. PMID 15084636. van Leeuwen F, Klokman W, Veer ... vinblastine and dacarbazine (ABVD) chemotherapy in the adult human ovary". Human Reproduction. doi:10.1093/humrep/dew260. PMID ...
October 2008). "Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: ... and dacarbazine, collectively known as CVD. Response to therapy is measured by a reduction in total tumor volume as well as ... and dacarbazine". Annals of Internal Medicine. 109 (4): 267-73. doi:10.7326/0003-4819-109-4-267. PMID 3395037. Huang H, Abraham ... and dacarbazine chemotherapy". The Journal of Clinical Endocrinology and Metabolism. 94 (8): 2850-6. doi:10.1210/jc.2008-2697. ...
Gershanovich ML, Akimov MA (2004). "[Chemoimmunotherapy with dacarbazine and aranose combined with interferon-alpha in ... together with dacarbazine and interferon-alpha in combination chemotherapy. During preclinical trials it also shown some ...
Other risk factors include the antiphospholipid syndrome, aspergillosis, Behçet's disease, dacarbazine, pregnancy, and trauma.[ ...
A study has shown that fotemustine produces improved response rates and but does not increase survival (over dacarbazine in the ... "Fotemustine Compared With Dacarbazine in Patients With Disseminated Malignant Melanoma: A Phase III Study". Journal of Clinical ...
... is contraindicated in people with hypersensitivity to it or to the similar drug dacarbazine. The use of ... MTIC, the active metabolite AIC (part of the naturally occurring AICA ribonucleotide) The related drug dacarbazine for ...
Dacarbazine, temozolomide, and cisplatin all have a reproducible 10-20% response rate in metastatic melanoma.[citation needed ...
"Bcl-2 Antisense (oblimersen sodium) Plus Dacarbazine in Patients With Advanced Melanoma: The Oblimersen Melanoma Study Group". ... dacarbazine) with or without Genasense. The initial size of this trial was expanded to enable a direct comparison of safety and ...
Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma ...
... Superior to Dacarbazine for Leiomyosarcoma, Liposarcoma FDA Approves Trabectedin (Yondelis) for Advanced Soft- ... after a phase III study comparing trabectedin with dacarbazine), the US FDA approved trabectedin (Yondelis) for the treatment ...
A phase III trial (vs dacarbazine) in patients with previously untreated metastatic melanoma showed an improved rates of ...
... or dacarbazine [DTIC]) in patients with advanced melanoma". Journal of Clinical Oncology. 26 (15_suppl): LBA9011. doi:10.1200/ ...
... or dacarbazine [DTIC]) in patients with advanced melanoma". Journal of Clinical Oncology. 26 (15S): LBA9011. doi:10.1200/jco. ...
April 2013). "Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a ...
"Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II ...
In the 152-patient trial, a combination of selumetinib and dacarbazine failed to improve progression-free survival compared ...
"Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II ...
Sellised ühendid on stabiilsemad kui näiteks Dacarbazine, mis on üks põhilisi nahavähi ravimeid. Imidasooli derivaatide hea ...
"Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma" at ... binimetinib had a median progression-free survival of 2.8 months versus 1.5 months for those on the standard dacarbazine ...
Common drugs that may cause a phototoxic reaction include amiodarone, dacarbazine, fluoroquinolones, 5-fluorouracil, furosemide ...
... dacarbazine. In clinical trials, B-Raf increased metastatic melanoma patient chance of survival. In spite of the drug's high ...
... compared to 8.4 months for participants treated with dacarbazine. Serious side effects may include a decrease in white blood ...
... dacarbazine, doxorubicin or by 'watchful waiting' and surgical debulking via Whipple procedure and other resections of the ...
... dacarbazine), BEACOPP, CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) and FAC (5-fluorouracil, ...
... and dacarbazine) versus A+AVD (a combination of brentuximab vedotin plus AVD, or doxorubicin, vinblastine, and dacarbazine) for ... dacarbazine (AVD) chemotherapy as a firstline treatment for advanced classical Hodgkin lymphoma. Brentuximab vedotin was ...
... dacarbazine MeSH D03.383.129.308.245 - dexmedetomidine MeSH D03.383.129.308.250 - econazole MeSH D03.383.129.308.253 - ...
"Dacarbazine". International Drug Price Indicator Guide. Retrieved 8 December 2016.. *^ British national formulary : BNF 69 (69 ... Dacarbazine (DTIC), also known as imidazole carboxamide, is a chemotherapy medication used in the treatment of melanoma and ... As of mid-2006, dacarbazine is commonly used as a single agent in the treatment of metastatic melanoma,[5][6] and as part of ... Dacarbazine works by methylating guanine at the O-6 and N-7 positions.[14] Guanine is one of the four nucleotides that makes up ...
Dacarbazine: learn about side effects, dosage, special precautions, and more on MedlinePlus ... Dacarbazine is used to treat melanoma (a type of skin cancer) that has spread to other parts of your body. Dacarbazine is also ... Before receiving dacarbazine,. *tell your doctor and pharmacist if you are allergic to dacarbazine, any other medications, or ... When dacarbazine is used to treat melanoma, it may be injected once a day for 10 days in a row every 4 weeks or it may be ...
Trabectedin may be better than dacarbazine for treatment of soft tissue sarcoma Janssen Research & Development, LLC announced ... AstraZeneca today announced that the Phase 3 SUMIT study of selumetinib in combination with dacarbazine for the treatment of ... The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment. ... vinblastine and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma patients in Japan. ...
Dacarbazine (or DTIC), is a chemotherapy drug used to treat Hodgkin lymphoma, melanoma and soft tissue sarcoma. It may also be ... What is dacarbazine (DTIC)?. Dacarbazine (DTIC) is used to treat melanoma, Hodgkin lymphoma and soft tissue sarcoma. It may ... How dacarbazine is given. You will be given dacarbazine in the chemotherapy day unit or during a stay in hospital. A ... Less common side effects of dacarbazine. Flu-like symptoms. Dacarbazine may cause flu-like symptoms such as having a headache ...
... in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with ... Conclusions: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus ... plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at ... of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P,0.001). No ...
... Learn about reported side effects ... Reported Side Effects for Dacarbazine 100mg Powder for Injection. Close Blood Clot Incidence: ,1.0%* Severity: SEVERE Onset: ... DACARBAZINE (da KAR ba zeen) is a chemotherapy drug. This medicine is used to treat skin cancer. It is also used with other ...
Bevacizumab vs Dacarbazine in Metastatic Melanoma. This study has been terminated. (Lack of financing of the study drug. Not ... Drug Information available for: Propranolol Dacarbazine Enalapril Enalapril maleate Enalaprilat Bevacizumab Genetic and Rare ... A Randomized Phase II Trial Comparing Bevacizumab Monotherapy With Dacarbazine (DTIC) in Treatment of Malignant Melanoma, ... Active Comparator: Dacarbazine Dacarbazine 1000mg/m2 q3w. Drug: Dacarbazine dacarbazine 1000 mg/m2 q3w ...
DBL Dacarbazine for Injection (Powder for injection) - Consumer Medicines Information leaflets of prescription and over-the- ... You must not be given DBL™ Dacarbazine for Injection if you have an allergy to dacarbazine or any of the ingredients listed at ... Tell your doctor or dentist if you intend having any dental work while being treated with dacarbazine. Dacarbazine may increase ... You should not be given DBL™ Dacarbazine for Injection if you are breast-feeding. It is not known whether dacarbazine passes ...
Dacarbazine (DTIC, DIC, imidazole carboxamide). Article Translations: (Spanish). How does this medicine work?. Dacarbazine (da- ... Blood counts begin to drop 3 to 7 days after dacarbazine is given and may be at their lowest 2 to 4 weeks after therapy. Blood ... Dacarbazine is given into the vein (IV) in the hospital or clinic. ... Sucking on hard candy while receiving dacarbazine may reduce an unpleasant taste. ...
"Dacarbazine" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... This graph shows the total number of publications written about "Dacarbazine" by people in Harvard Catalyst Profiles by year, ... Brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine for nonbulky limited-stage classical Hodgkin lymphoma. Blood. ... Below are the most recent publications written about "Dacarbazine" by people in Profiles. ...
... is a brand of medicine containing the active ingredient Dacarbazine. Find out about side effects, who ca... ... How DBL™ Dacarbazine for Injection is given. How much is given. Your doctor will decide what dose of dacarbazine you will ... DBL™ Dacarbazine for Injection is available only with a doctors prescription.. Before you are given DBL™ Dacarbazine for ... What DBL™ Dacarbazine for Injection is used for. Dacarbazine belongs to a group of medicines known as antineoplastic or ...
Dacarbazine, DTIC injection. What is this medicine?. DACARBAZINE (da KAR ba zeen) is a chemotherapy drug. This medicine is used ... an unusual or allergic reaction to dacarbazine, other chemotherapy agents, other medicines, foods, dyes, or preservatives ...
Dacarbazine was used as the comparator drug in both Phase III pivotal trials. Since patient characteristics of the dacarbazine ... and dacarbazine [32]. They found an ICER for vemurafenib compared to dacarbazine of $353,993/QALY, which is comparable to our ... median age 53 years) or dacarbazine (. , median age 50 years) and had a median time on study of 4.9 months. In both trials, ... and tenfold more expensive than dacarbazine even when including a prophylactic antiemetic regimen with dacarbazine. However, we ...
... inserted into a large vein under the skin of the chest or through a vein in the arm to receive dacarbazine. Dacarbazine will be ... inserted into a large vein under the skin of the chest or through a vein in the arm to receive dacarbazine. Dacarbazine will be ... Dacarbazine starting Dose 250 mg/m^2 a day on Days 1-3 of 21 Day Cycle. Imatinib starting Dose 400 mg a day on Days 1-21 of 21 ... Imatinib in Combination With Dacarbazine and Capecitabine in Medullary Thyroid Carcinoma. The safety and scientific validity of ...
Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma (SICOG 0109). The safety and ... Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma: Phase III Study. ... Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant ... Drug Information available for: Dacarbazine Interferon Genetic and Rare Diseases Information Center resources: Neuroendocrine ...
This is a combination Phase I/II design that explores the toxicity and activity of Sunitinib and Dacarbazine (DTIC) for ... A Phase I/II Study of Sunitinib and Dacarbazine in Patients With Metastatic Melanoma. Trial Phase:. Phase 1/Phase 2. Minimum ... combination of sunitinib and Dacarbazine (DTIC) for metastatic melanoma. Screening tests. (pre-study) will consist of a history ... A Phase I/II Study of Sunitinib and Dacarbazine in Patients With Metastatic Melanoma ...
Market Research Report 2018 aims at providing comprehensive data on dacarbazine market globally and regionally (Europe, ... Dacarbazine prices in North America. 6.4. Dacarbazine prices in other regions. 7. DACARBAZINE END-USE SECTOR 7.1. Dacarbazine ... Dacarbazine market forecast. 6. DACARBAZINE MARKET PRICES. 6.1. Dacarbazine prices in Europe. 6.2. Dacarbazine prices in Asia ... Dacarbazine application spheres, downstream products. 3. DACARBAZINE MANUFACTURING METHODS. 4. DACARBAZINE PATENTS. Abstract. ...
Zetoony on dacarbazine adverse effects: Interferon can cause many different types of side-effects including anemia, low white ...
Drug: Cabozantinib S-malate Drug: Dacarbazine Other: Laboratory Biomarker Analysis Drug: Temozolomide Phase 2 ... Drugs used in chemotherapy, such as temozolomide and dacarbazine, work in different ways to stop the growth of tumor cells, ... If temozolomide is not available, patients receive dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in ... Dacarbazine. Imidazole. Antineoplastic Agents, Alkylating. Alkylating Agents. Molecular Mechanisms of Pharmacological Action. ...
A peptide-modified solid lipid nanoparticle formulation of paclitaxel modulates immunity and outperforms dacarbazine in a ... A peptide-modified solid lipid nanoparticle formulation of paclitaxel modulates immunity and outperforms dacarbazine in a ... PSM exerts more apoptotic and anti-invasive effects in B16F10 mice melanoma cells as compared to dacarbazine (DTIC), an ...
Inhibitory Effects and Mechanism analysis on the Inhibition of Dacarbazine on Melanoma Stem Cells Proliferation in vitro ... Inhibition of Dacarbazine on Melanoma Stem Cells. Info: 3256 words (13 pages) Essay. Published: 14th May 2018 in Biology ... Dacarbazine (DTIC), which can be used in a variety of cancers including fibrosarcoma [4], Hodgkins disease [5], lung cancer [6 ... Key words: melanoma; dacarbazine; microRNA; stem cell Introduction Melanoma is a kind of malignant tumor with an increasing ...
... Andersson, Ronny Umeå ... Malignant melanoma, interferon-[alpha], verapamil, dacarbazine Identifiers. URN: urn:nbn:se:umu:diva-30093OAI: oai:DiVA.org:umu ... Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-[alpha] (IFN[alpha]) as single ...
Reduced efficacy of dacarbazine possible due to inhibition of the conversion of dacarbazine to its active metabolite (which may ... Increased toxicity of dacarbazine metabolite possible due to hastened and/or higher percentage of dacarbazine activation. Avoid ... Dacarbazine: TGA approved but not PBS reimbursed. Cost:. ~ $550 per cycle "How this cost is calculated" The cost displayed on ... Dacarbazine: TGA approved but not PBS reimbursed. Cost:. ~ $550 per cycle "How this cost is calculated" The cost displayed on ...
PubMed journal article Reduction of Dacarbazine cytogenetic effects on somatic cells in male mice using bee glue (Propolis) to ... and Dacarbazine-treated group (treated with 3.5mg/kg Dacarbazine). The fourth, fifth, and sixth were treated with Dacarbazine ... and Dacarbazine-treated group (treated with 3.5mg/kg Dacarbazine). The fourth, fifth, and sixth were treated with Dacarbazine ... Reduction of Dacarbazine cytogenetic effects on somatic cells in male mice using bee glue (Propolis) to manifest the scientific ...
Dabrafenib Dacarbazine Dacogen® Dactinomycin Daratumumab Darbepoetin Alfa Darzalex® Dasatinib Daunorubicin Daunorubicin and ... Phase III randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) versus DTIC alone as first-line treatment in patients ... Phase III randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) versus DTIC alone as first-line treatment in patients ...
Dacarbazine alone was ineffective at 80 mg/kg/dose IP. Combination therapy was not superior to PNT2258 alone. In contrast, ... Abstract 2764: Effect of PNT2258 combinations with docetaxel, dacarbazine, or vemurafenib on the A375 melanoma xenograft. Wendi ... Overall, 1) PNT2258+docetaxel produced a greater than additive effect compared to single agents, 2) PNT2258+dacarbazine was not ... Abstract 2764: Effect of PNT2258 combinations with docetaxel, dacarbazine, or vemurafenib on the A375 melanoma xenograft ...
A Phase I, Open Label, Study of the Safety and Tolerability of KU-0059436 and Dacarbazine in the Treatment of Patients With ... A Phase I, Open Label, Study of the Safety and Tolerability of KU-0059436 and Dacarbazine in the Treatment of Patients With ... To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436 in combination with dacarbazine. ...
Dacarbazine toxicity in murine liver cells: a model of hepatic endothelial injury and glutathione defense.. L D Deleve ... Dacarbazine toxicity in murine liver cells: a model of hepatic endothelial injury and glutathione defense.. L D Deleve ... Dacarbazine toxicity in murine liver cells: a model of hepatic endothelial injury and glutathione defense.. L D Deleve ... Dacarbazine (5-(3,3-dimethyl-triazeno) imidazole-4-carboxamide), 3 and 6 mM, was toxic to SECs but not to hepatocytes. Onset of ...
Background: The role of bleomycin and dacarbazine in the ABVD regimen (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine ... Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkins lymphoma ... Interpretation: Dacarbazine cannot be omitted from ABVD without a substantial loss of efficacy. With respect to our predefined ... We aimed to investigate whether omission of either bleomycin or dacarbazine, or both, from ABVD reduced the efficacy of this ...
  • We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. (nih.gov)
  • We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. (nih.gov)
  • Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. (nih.gov)
  • Until 2011, dacarbazine, a chemotherapeutic alkylating agent, was the standard of care for patients with metastatic melanoma despite its lack of survival benefit [ 7 , 8 ]. (hindawi.com)
  • This is a combination Phase I/II design that explores the toxicity and activity of a combination of sunitinib and Dacarbazine (DTIC) for metastatic melanoma. (knowcancer.com)
  • In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma. (aacrjournals.org)
  • The repeated administration of L19-IL2 in combination with dacarbazine is safe and shows encouraging signs of clinical activity in patients with metastatic melanoma. (aacrjournals.org)
  • This article presents clinical evidence that the combination of dacarbazine with the tumor-targeting immunocytokine L19-IL2 (a biopharmaceutical consisting of the human recombinant antibody L19, specific to the alternatively spliced EDB domain of fibronectin, fused to human interleukin-2) is well tolerated in patients with metastatic melanoma and can induce long-lasting objective responses in a subset of patients. (aacrjournals.org)
  • Despite such modest efficacy, dacarbazine still represents the reference treatment of metastatic melanoma, chosen as comparative arm in many clinical trials ( 8 ). (aacrjournals.org)
  • Conclusion: Extended schedule escalated dose Temozolomide (7 days on 7 days off) is feasible and has an acceptable safety profile, but does not improve OS and PFS in metastatic melanoma when compared to standard dose dacarbazine. (eur.nl)
  • Sorafenib-dacarbazine combination shows activity in metastatic melanoma. (northwestern.edu)
  • Materials and methods: Peripheral blood lymphocytes from patients with metastatic melanoma undergoing dacarbazine chemotherapy every 21 days for a total of 7 cycles, were analysed for the presence of micronuclei with the CREST antikinetochore antibody technique. (elsevier.com)
  • Luikart, SD & Kirkwood, JM 1982, ' A comparison of vinblastine/bleomycin/Cis-platin (VBD) with dacarbazine (DTIC) in metastatic melanoma ', Proceedings of the American Society of Clinical Oncology , vol. (umn.edu)
  • Seattle Genetics, Inc. today announced that its collaborator, Takeda Pharmaceutical Company Limited, has received approval from the Japanese Ministry of Health, Labour and Welfare for ADCETRIS (brentuximab vedotin) in combination with doxorubicin, vinblastine and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma patients in Japan. (news-medical.net)
  • Recently published results of a phase 2 clinical trial have shown the best outcomes to date for newly diagnosed older Hodgkin lymphoma patients treated with brentuximab vedotin given before and after doxorubicin, vinblastine and dacarbazine chemotherapy, which is the standard of care. (news-medical.net)
  • Background: The role of bleomycin and dacarbazine in the ABVD regimen (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) has been questioned, especially for treatment of early-stage favourable Hodgkin's lymphoma, because of the drugs' toxicity. (mdc-berlin.de)
  • We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). (uzh.ch)
  • A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time. (uzh.ch)
  • Doxorubicin and dacarbazine chemotherapy was started after a left above-knee amputation. (freethesaurus.com)
  • Studies have shown that dacarbazine (DTIC)-doxorubicin (DOX) (D-D) therapy is the most effective treatment. (elsevier.com)
  • ABVD (doxorubicin, bleomycin, vinblastine (Vb) and dacarbazine) is the standard regimen inHodgkin's lymphoma (HL).Vincristine (O) is a mitotic spindle agent like Vb. (waocp.org)
  • We present updated efficacy and safety analyses in high-risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON-1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first-line therapy after a median follow-up of 37.1 months. (openrepository.com)
  • Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. (wikipedia.org)
  • Phase III randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) versus DTIC alone as first-line treatment in patients with unresectable stag. (oncolink.org)
  • Secondary end points included overall survival and objective response rate.Results: A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or placebo plus dacarbazine (n = 32). (uni-muenchen.de)
  • In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median, 2.8 v 1.8 months);the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27;two-sided P = .32). (uni-muenchen.de)
  • The objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus dacarbazine (two-sided P = .36). (uni-muenchen.de)
  • The most frequently reported adverse events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash (57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%).Conclusion: In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety profile but did not significantly improve PFS compared with placebo plus dacarbazine. (uni-muenchen.de)
  • Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. (aacrjournals.org)
  • Genasense plus dacarbazine yielded superior results in a large randomized trial," said Dr. (freethesaurus.com)
  • Genasense, the company's lead compound, has received "Fast Track" designation from the Food and Drug Administration, and the combination of Genasense plus dacarbazine is currently undergoing a Phase 3 trial in patients with advanced melanoma. (freethesaurus.com)
  • Brentuximab Vedotin Plus Dacarbazine or Bendamustine: New Options for Older Patients with Hodgkin Lymphoma? (ashclinicalnews.org)
  • At the time of data presentation, 60 patients had been treated: 27 with brentuximab vedotin monotherapy, 22 with brentuximab vedotin plus dacarbazine, and 11 with brentuximab vedotin plus bendamustine. (ashclinicalnews.org)
  • A Randomized Phase II Trial Comparing Bevacizumab Monotherapy With Dacarbazine (DTIC) in Treatment of Malignant Melanoma, Focusing on Angiogenic Markers and Prevention of Hypertension. (clinicaltrials.gov)
  • Dacarbazine is used alone or in combination with other antineoplastic medications to treat metastatic malignant melanoma (a type of skin cancer). (canoe.com)
  • Dacarbazine is used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas. (selfdecode.com)
  • Dacarbazine (DTIC) is an alkylating chemotherapy medication that is used to treat Hodgkin lymphoma and malignant melanoma . (dvohmg.com)
  • DTIC (Dacarbazine) is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas. (comprar-medicina.com)
  • Dacarbazine is used for treating certain types of cancer, such as skin cancer that has spread (metastatic malignant melanoma). (medsdelta.com)
  • To compare the effectiveness of dacarbazine with or without oblimersen (G3139) in treating patients who have advanced malignant melanoma. (isrctn.com)
  • O6-Alkylguanine-DNA alkyltransferase (ATase) levels were measured in peripheral blood lymphocytes of 13 patients with advanced malignant melanoma treated with sequential dacarbazine (DTIC) and fotemustine. (openrepository.com)
  • NEMO: A phase 3 trial of binimetinib (MEK162) versus dacarbazine in patients with advanced NRAS-mutant melanoma who are untreated or have progresse. (esmo.org)
  • The recommended dacarbazine dosage will be different for each person, depending on his or her weight, the reason the medicine is being used, and a number of other factors. (emedtv.com)
  • What Is the Recommended Dacarbazine Dosage for Treating Melanoma? (emedtv.com)
  • The usual recommended dosage of dacarbazine for treating Hodgkin's disease is 150 mg per m 2 daily for 5 days. (emedtv.com)
  • Detailed information related to Dacarbazine Injection's uses, composition, dosage, side effects and reviews is listed below. (aviencepharma.com)
  • The recommended dosage of Dacarbazine for Injection in the treatment of Hodgkin's disease is 150 mg/square meter body surface/day for 5 days, in combination with other effective drugs. (pfizermedicalinformation.co.nz)
  • Dosage and cycle effects of dacarbazine (DTIC) and fotemustine on O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells. (openrepository.com)
  • We aimed to investigate whether omission of either bleomycin or dacarbazine, or both, from ABVD reduced the efficacy of this regimen in treatment of Hodgkin's lymphoma. (mdc-berlin.de)
  • Interpretation: Dacarbazine cannot be omitted from ABVD without a substantial loss of efficacy. (mdc-berlin.de)
  • Each vial of sterile lyophilized powder for reconstitution contains dacarbazine 600 mg. (canoe.com)
  • Each vial contains 200 mg of dacarbazine (the active ingredient), citric acid monohydrate and mannitol. (pfizermedicalinformation.com.tn)
  • Dacarbazine for Injection 200 mg/vial is reconstituted with 19.7 mL of Sterile Water for Injection, USP. (pfizermedicalinformation.co.nz)
  • Dacarbazine ( DTIC ), also known as imidazole carboxamide , is a chemotherapy medication used in the treatment of melanoma and Hodgkin's lymphoma . (wikipedia.org)
  • Treatment regimen included orally administered sorafenib and intravenous dacarbazine. (uzh.ch)
  • Patients and methods: A total of 859 patients were randomised to receive oral temozolomide at 150 mg/m2/day for seven consecutive days every 2 weeks or dacarbazine, administered as an intravenous infusion at 1000 mg/m2/day on day 1 every 3 weeks. (eur.nl)
  • After intravenous administration of Dacarbazine for Injection, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. (pfizermedinfo.co.kr)
  • Dacarbazine is an intravenous chemotherapy used alone or in combination with other agents for the treatment of certain types of cancer. (nccs.com.sg)
  • Before taking Dacarbazine, what precautions must I follow? (nccs.com.sg)
  • The extended schedule, escalated dose temozolomide arm showed more toxicity than the standard dose, single agent dacarbazine arm. (eur.nl)
  • The standard treatment of advanced melanoma has for many years been single-agent dacarbazine (DTIC). (freethesaurus.com)
  • This medication has not been studied in pregnant women, but it is possible that it may also cause birth defects in babies whose mothers received dacarbazine injection during pregnancy. (medlineplus.gov)
  • It is therefore recommended that any dental work be completed prior to starting dacarbazine treatment. (mydr.com.au)
  • When used to treat Hodgkin's lymphoma, dacarbazine is used in combination with other medicines, regardless of the amount used. (emedtv.com)
  • tell your doctor and pharmacist if you are allergic to dacarbazine, any other medications, or any of the ingredients in dacarbazine injection. (medlineplus.gov)
  • You must not be given DBL™ Dacarbazine for Injection if you have an allergy to dacarbazine or any of the ingredients listed at the end of this leaflet. (mydr.com.au)
  • The following is a list of possible side-effects that may occur from all constituting ingredients of Dacarbazine Injection. (aviencepharma.com)
  • Ingredients Dacarbazine Injection 100 , 200 , 500 and 1000 mg. (medwiseoverseas.in)
  • Liver damage may occur more often in people that are receiving other cancer chemotherapy drugs along with dacarbazine treatment. (medlineplus.gov)
  • You should not use dacarbazine injection while you are pregnant or plan to become pregnant unless your doctor decides that this is the best treatment for your condition. (medlineplus.gov)
  • Probabilistic sensitivity analysis showed that, at a willingness-to-pay (WTP) threshold of ≤$100,000/QALY, dacarbazine was the optimal treatment in ~85% of simulations. (hindawi.com)
  • If you are found to be eligible to take part in this study, you will begin treatment with imatinib mesylate, capecitabine, and dacarbazine. (clinicaltrials.gov)
  • The fourth, fifth, and sixth were treated with Dacarbazine and Propolis as pre 2h, post 2h, and concomitant treatment. (unboundmedicine.com)
  • The in vivo studies revealed that Dacarbazine induced an abnormalities in polychromatic erythrocytes cells (PECs) as increase of cell with micronuclei, while the dual treatment accompanied with improvement of this abnormalities. (unboundmedicine.com)
  • Demetri says recent studies have revealed that dacarbazine is much more useful in the treatment of leiomyosarcomas than initially thought. (targetedonc.com)
  • Biopsies of skin or superficial lymph node metastases were taken before treatment (baseline), during sorafenib and after dacarbazine therapy and used for transcriptional profiling and validation experiments. (uzh.ch)
  • Our data reveal in situ changes in melanoma metastases during treatment with sorafenib and dacarbazine and suggest an additional mechanism of action through immunomodulation. (uzh.ch)
  • Cisplatin treatment of melanoma cells resulted in an induction of apoptosis as demonstrated by flow cytometry (accumulation of cells at the subG1 phase of the cell cycle), whereas dacarbazine caused G1/G0 cell cycle arrest, with the effects being improved by pre‑treatment with vitamin D analogs. (spandidos-publications.com)
  • Dacarbazine caused transient stimulation of ROS levels and the mitochondrial membrane potential (Δψm) (after 1 or 3 h of treatment, respectively), but the effect was not detectable following prolonged (24 h) incubation with the drug. (spandidos-publications.com)
  • however, only a minority of patients with melanoma respond to dacarbazine treatment. (aacrjournals.org)
  • Dacarbazine is commonly administered for the treatment of cancers prevalent in reproductive age females. (monash.edu)
  • Importantly, diminished ovarian reserve can result in premature ovarian insufficiency and infertility, thus, fertility preservation options should be considered for young female patients prior to dacarbazine treatment. (monash.edu)
  • In a retrospective study we analysed the levels of the DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) in melanoma metastases in patients receiving dacarbazine (DTIC) either as a single drug or as part of combination chemotherapy regimens, and related the expression levels to the clinical response to treatment. (ovid.com)
  • Before you begin treatment with dacarbazine, you and your doctor should talk about the good dacarbazine will do as well as the risks of using it. (drugster.info)
  • July 22, 2015 /PRNewswire/ -- AstraZeneca today announced that the Phase 3 SUMIT study of selumetinib in combination with dacarbazine for the treatment of patients with metastatic uveal melanoma did not meet its primary endpoint of progression free survival. (freethesaurus.com)
  • Let your healthcare provider know if you experience anything that doesn't seem right during dacarbazine treatment. (emedtv.com)
  • Dacarbazine Injection is a medicine that is used for the treatment of Skin Cancer, Cancer Of White Blood Cells, Cancer Of Soft Tissues and other conditions. (aviencepharma.com)
  • It is advisable for men undergoing dacarbazine treatment to take contraceptive measures during and for 6 months after termination of therapy. (heethealthcare.co.in)
  • Do not drink alcohol while on dacarbazine treatment. (heethealthcare.co.in)
  • Patients in the dacarbazine group received a median of 11.5 treatment cycles, those in the monotherapy group had received a median of eight cycles, and the median duration of treatment had not yet been defined for the brentuximab vedotin plus bendamustine cohort. (ashclinicalnews.org)
  • Brentuximab vedotin in combination with dacarbazine or bendamustine for frontline treatment of Hodgkin lymphoma in patients aged 60 years and above: interim results of a multi-cohort phase 2 study. (ashclinicalnews.org)
  • Overall, 1) PNT2258+docetaxel produced a greater than additive effect compared to single agents, 2) PNT2258+dacarbazine was not superior to PNT2258 alone, 3) PNT2258+vemurafenib while highly active, was not superior to vemurafinib therapy alone, and 4) therapeutic PNT2258 exposures have been attained in patients. (aacrjournals.org)
  • Dacarbazine (5-(3,3-dimethyl-triazeno) imidazole-4-carboxamide), 3 and 6 mM, was toxic to SECs but not to hepatocytes. (aspetjournals.org)
  • Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine. (selfdecode.com)
  • Price of Dacarbazine EP Impurity C, VENDOR OF Dacarbazine IMPURITIES, CAS: NA, 5-diazenyl-1H-imidazole-4-carboxamide SUPPLIER, Dacarbazine impurity manufacturer. (synthinkchemicals.com)
  • This study presents data indicating that nanomolar concentrations of the hormonally active form of vitamin D, 1α,25‑dihydroxyvitamin D3 [1α,25(OH)2D3], its non‑calcemic analogues 20S‑hydroxyvitamin D3 and 21‑hydroxypregnacalciferol, as well as the low‑calcemic synthetic analog calcipotriol, modulate the efficacy of the anticancer drugs cisplatin and dacarbazine. (spandidos-publications.com)
  • On the other hand, only 1α,25(OH)2D3 resulted in a minor, but significant effect on the proliferation of melanoma cells treated simultaneously with dacarbazine, but not cisplatin. (spandidos-publications.com)
  • Notably, cisplatin (300 µM) exhibited a higher overall antiproliferative activity than dacarbazine. (spandidos-publications.com)
  • Finally, cisplatin, dacarbazine and 1α,25(OH)2D3 displayed modulatory effects on the expression of ROS and vitamin D‑associated genes in the melanoma A375 cells. (spandidos-publications.com)
  • Patients received cisplatin, vinblastine, and dacarbazine (CVD: cisplatin (20 mg/m 2 ) and vinblastine (1.2 mg/m 2 ) on days 1-4, dacarbazine (800 mg/m 2 ) on day 1 only) concurrently with interleukin 2 (9 MIU/m 2 /day) by continuous i.v. infusion on days 1-4 and IFN-α (5 MU/m 2 /day) on days 1-5, 8, 10, and 12. (aacrjournals.org)
  • This study was carried out to investigate the ability of Propolis to ameliorate the adverse cytogenetic effects of Dacarbazine on bone marrow cells. (unboundmedicine.com)
  • It could be concluded that there are protective effects of Propolis against the adverse effects of Dacarbazine. (unboundmedicine.com)
  • However, investigations of off-target effects of dacarbazine on the ovary are limited. (monash.edu)
  • Some of the possible side effects of dacarbazine can include loss of appetite, vomiting, and hair loss. (emedtv.com)
  • Some side effects of dacarbazine are potentially serious and should be reported immediately to your healthcare provider. (emedtv.com)
  • In conclusion, our results have shown that dacarbazine induced chromosome loss in lymphocytes from patients treated with this drug. (elsevier.com)
  • The IFNγ-induced gene signature seemed to be enhanced after addition of dacarbazine to sorafenib. (uzh.ch)
  • Serum IFNγ also increased during therapy, particularly after addition of dacarbazine. (uzh.ch)
  • While previous studies have indicated that single-agent brentuximab vedotin is safe and effective for these patients, other trials have suggested that its efficacy may be improved by the addition of dacarbazine or bendamustine. (ashclinicalnews.org)
  • To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436 in combination with dacarbazine. (knowcancer.com)
  • Dacarbazine toxicity in murine liver cells: a model of hepatic endothelial injury and glutathione defense. (aspetjournals.org)
  • The relative resistance to dacarbazine toxicity seen in hepatocytes is not due to more efficient GSH detoxification, because toxicity was not unmasked in hepatocytes cultures in medium lacking sulfur amino acid precursors of GSH. (aspetjournals.org)
  • Hemopoietic depression is the most common toxicity with dacarbazine for injection. (drugster.info)
  • This product offered by SynThink is generally used for ANDA , DMF filing, toxicity study of respective drug formulation, Quality Control (QC) of Dacarbazine manufacturing. (synthinkchemicals.com)
  • Background: A phase II study of dacarbazine (DTIC), was conducted to determine the response rate, duration of response, toxicity and overall survival of patients with advanced pancreatic islet cell tumors. (elsevier.com)
  • Hemopoietic depression is the most common toxicity with Dacarbazine for Injection and involves primarily the leukocytes and platelets, although, anemia may sometimes occur. (pfizermedicalinformation.com.ve)
  • Hemopoietic toxicity may warrant temporary suspension or cessation of therapy with Dacarbazine for Injection. (pfizermedicalinformation.com.ve)
  • This toxicity has been observed mostly when Dacarbazine for Injection has been administered concomitantly with other anti-neoplastic drugs: however, it has also been reported in some patients treated with Dacarbazine for Injection alone. (pfizermedicalinformation.com.ve)
  • Dacarbazine alone was ineffective at 80 mg/kg/dose IP. (aacrjournals.org)
  • The recommended dose of L19-IL2 in combination with dacarbazine was defined as 22.5 Mio IU. (aacrjournals.org)
  • Purpose: To compare the efficacy of an extended schedule escalated dose of temozolomide versus standard dose dacarbazine in a large population of patients with stage IV melanoma. (eur.nl)
  • Dacarbazine was used as a control drug and was administered for five consecutive days at a dose of 80 mg/kg. (anavex.com)
  • The recommended dose of dacarbazine is based on body weight or body size. (canoe.com)
  • The appropriate dose of dacarbazine is often given once daily for 5 or 10 days depending on the dose. (canoe.com)
  • The usual recommended dose of dacarbazine for treating melanoma ( skin cancer ) is 2 to 4.5 mg per kg body weight (about 0.09 to 2.04 mg per lb) once a day for 10 days. (emedtv.com)
  • The usual recommended dose of dacarbazine based on body surface area is 250 mg per m 2 daily for 5 days. (emedtv.com)
  • The average cumulative excretion of unchanged dacarbazine in the urine is 40% of the injected dose in 6 hours. (pfizermedinfo.co.kr)
  • These studies were undertaken to determine the initial cellular target and the role of glutathione detoxification of dacarbazine, a toxin implicated in hepatic veno-occlusive disease. (aspetjournals.org)
  • Dacarbazine belongs to a group of medicines known as antineoplastic or cytotoxic agents. (mydr.com.au)
  • Description: Dacarbazine is a triazene derivative with antineoplastic activity. (bet-bromodomain.com)
  • You will be given dacarbazine in the chemotherapy day unit or during a stay in hospital. (macmillan.org.uk)
  • You should not be given dacarbazine if you are pregnant or intend to become pregnant. (mydr.com.au)
  • If temozolomide is not available, patients receive dacarbazine intravenously (IV) over 15-60 minutes on day 1. (clinicaltrials.gov)
  • 1. Patients in group one will receive dacarbazine once every 3 weeks for up to eight courses in the absence of disease progression. (isrctn.com)
  • Dacarbazine, Westren Medicine, Western Drug manufacturer / supplier in China, offering 99.6% High Purity Powder Daunorubicin Hydrochloride (CAS: 23541-50-6) 20mg, High Purity Sertraline HCl Sertraline Hydrochloride 79559-97-0 Tablet and Capsule Garde, Hydrocortisone Sodium Succinate Powder for Injection GMP Factory FDA Approved and so on. (made-in-china.com)
  • How important is bleomycin in the adriamycin + bleomycin + vinblastine + dacarbazine regimen? (semanticscholar.org)
  • article{Canellos2004HowII, title={How important is bleomycin in the adriamycin + bleomycin + vinblastine + dacarbazine regimen? (semanticscholar.org)
  • Like many chemotherapy drugs, dacarbazine may have numerous serious side effects, because it interferes with normal cell growth as well as cancer cell growth. (wikipedia.org)
  • Dacarbazine is considered to be highly emetogenic , [12] and most patients will be pre-medicated with dexamethasone and antiemetic drugs like 5-HT 3 antagonist (e.g., ondansetron ) and/or NK 1 receptor antagonist (e.g., aprepitant ). (wikipedia.org)
  • Dacarbazine can be given in combination with other cancer drugs. (macmillan.org.uk)
  • Capecitabine and dacarbazine are drugs that interfere with the growth of cancer cells. (clinicaltrials.gov)
  • Drugs used in chemotherapy, such as temozolomide and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. (clinicaltrials.gov)
  • Dacarbazine injection comes as a powder to be mixed with liquid to be injected intravenously (into a vein) over 1 minute or infused intravenously over 15 to 30 minutes by a doctor or nurse in a medical facility. (medlineplus.gov)
  • Dacarbazine for Injection, USP is reconstituted and administered intravenously (pH 3 to 4). (pfizermedicalinformation.com.tn)
  • abstract = "Background: Dacarbazine is an antitumour drug used with considerable success in the chemotherapy of a number of human neoplasias, particularly advanced disseminated melanoma. (elsevier.com)
  • Tell your doctor if you have ever had any unusual or allergic reaction to dacarbazine or any other medicines. (drugster.info)
  • Dacarbazine is used to treat melanoma (a type of skin cancer) that has spread to other parts of your body. (medlineplus.gov)
  • When dacarbazine is used to treat melanoma, it may be injected once a day for 10 days in a row every 4 weeks or it may be injected once a day for 5 days in a row every 3 weeks. (medlineplus.gov)
  • Dacarbazine (DTIC) is a chemotherapy drug used to treat melanoma, Hodgkin lymphoma and soft tissue sarcoma. (macmillan.org.uk)
  • Significantly, Dacarbazine, a currently available chemotherapy drug used to treat melanoma and other types of cancer, was found to be completely inactive in the same tests. (anavex.com)
  • PSM exerts more apoptotic and anti-invasive effects in B16F10 mice melanoma cells as compared to dacarbazine (DTIC), an approved chemotherapeutic drug for treating aggressive melanoma. (rsc.org)
  • It is recommended that dacarbazine for injection be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. (drugster.info)
  • DACARBAZINE (da KAR ba zeen) is a chemotherapy drug. (cvs.com)
  • In a recent phase II, frontline, open-label study, Christopher A. Yasenchak, MD , from the Willamette Valley Cancer Institute and Research Center/US Oncology Research in Springfield, Oregon, and colleagues examined the efficacy and durability of brentuximab vedotin as a single-agent and in combination with dacarbazine or bendamustine in patients with HL ≥60 years old. (ashclinicalnews.org)
  • Dacarbazine often causes nausea and vomiting, but it is important to keep using this medication even if you feel ill, unless otherwise directed by your doctor. (canoe.com)
  • To determine the maximum tolerated doses (MTD) for the combination of imatinib mesylate, capecitabine, and dacarbazine in patients with solid tumors. (clinicaltrials.gov)
  • To determine the overall tumor response rate to imatinib mesylate in combination with capecitabine and dacarbazine as first line and second line therapy in advanced metastatic medullary thyroid carcinoma. (clinicaltrials.gov)
  • Sorafenib is a multi-kinase inhibitor used alone or in combination with dacarbazine to treat metastasized melanoma. (uzh.ch)
  • The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m 2 of dacarbazine on day 1 of a 3-weekly therapy cycle. (aacrjournals.org)
  • CD34+ cells were firstly amplified 20-fold Dacarbazine by a combination of TPO SCF and Flt-3 and then they were cultured with HGF and FGF4. (healthweblognews.info)
  • Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. (harvard.edu)
  • Transition probabilities were derived from two Phase III registration trials comparing each BRAF inhibitor against dacarbazine. (hindawi.com)
  • This randomized phase II trial studies how well cabozantinib-s-malate works compared with temozolomide or dacarbazine in treating patients with melanoma of the eye (ocular melanoma) that has spread to other parts of the body and cannot be removed by surgery. (clinicaltrials.gov)
  • In this phase 3 clinical trial, when Genasense was combined with dacarbazine , the most frequent serious adverse event occurring in more than 5 percent of patients was fever (5. (freethesaurus.com)
  • Dacarbazine is not cell cycle-phase specific. (selfdecode.com)
  • Phase II trial dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. (elsevier.com)
  • Fingerprint Dive into the research topics of 'Phase II trial dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. (elsevier.com)
  • [1] Dacarbazine is in the alkylating agent and purine analog families of medication. (wikipedia.org)
  • Dacarbazine is bioactivated in liver by demethylation to "MTIC" and then to diazomethane , which is an alkylating agent. (wikipedia.org)
  • Until the recent approval of ipilimumab and vemurafenib, the melanoma therapy landscape was dominated by two agents, dacarbazine and interleukin-2 ( 4, 5 ). (aacrjournals.org)
  • It has been compared to dacarbazine (DTIC), standard melanoma therapy, in a clinical trial with longer follow-up than the ipilimumab trial. (freethesaurus.com)
  • Dacarbazine belongs to the group of medicines called alkylating agents. (drugster.info)
  • Your doctor will order certain tests to check your body's response to dacarbazine. (medlineplus.gov)
  • Dacarbazine can cause anemia and reduce the body's ability to fight infections. (dvohmg.com)
  • There are also generic versions of dacarbazine available from APP, Bedford, Mayne Pharma (now Hospira ) and Teva . (wikipedia.org)
  • NDA 075940 describes DACARBAZINE , which is a drug marketed by Abraxis Pharm , Fresenius Kabi Usa , Hospira , Teva Pharms Usa , and West-ward Pharms Int , and is included in six NDAs. (drugpatentwatch.com)
  • hospira inc. received approval authorities for arresting its dacarbazine modified capsules in early january, but the company has reportedly needed considerable time to build oneself up an adequate supply of the drug growing and to reach in thee a comarketing agreement with another large pharmaceutical manufacturer. (victoriangraceart.com)