DiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentInformation ScienceHealth Care
DacarbazineMelanomaVinblastineBleomycinMechlorethamineHodgkin DiseaseAntineoplastic Agents, AlkylatingProcarbazineAntineoplastic Combined Chemotherapy ProtocolsDoxorubicinSkin NeoplasmsVincristineNitrosourea CompoundsNimustineCarmustineMesnaLomustineInterferon-alphaCombined Modality TherapyPrednisoneO(6)-Methylguanine-DNA MethyltransferaseDisease-Free SurvivalTreatment OutcomeCisplatinChillsBenzenesulfonatesSurvival AnalysisHexanonesAntineoplastic AgentsTamoxifenNeoplasm MetastasisSarcomaAdministration, IntravenousCyclophosphamideDrug Administration ScheduleNeoplasm StagingPhenylurea CompoundsNiacinamideEtoposideVindesineIfosfamideDNA Modification MethylasesOrganophosphorus CompoundsSurvival RateMelanoma, ExperimentalKaplan-Meier EstimateInterleukin-2GuanineRemission InductionDisease ProgressionPheochromocytoma
Dacarbazine: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)Melanoma: 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)Vinblastine: Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)Bleomycin: 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.Mechlorethamine: 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.Hodgkin Disease: 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.Antineoplastic Agents, Alkylating: 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)Procarbazine: An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease.Antineoplastic Combined Chemotherapy Protocols: 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.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Skin Neoplasms: Tumors or cancer of the SKIN.Vincristine: An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)Nitrosourea CompoundsNimustine: 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.Carmustine: 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)Mesna: A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors.Interferon-alpha: 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.Combined Modality Therapy: 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.Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.O(6)-Methylguanine-DNA Methyltransferase: 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.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.Treatment Outcome: 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.Cisplatin: 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.Chills: The sudden sensation of being cold. It may be accompanied by SHIVERING.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.Survival Analysis: 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.Hexanones: 6-carbon straight-chain or branched ketones.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Tamoxifen: 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.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.Administration, Intravenous: Delivery of substances through VENIPUNCTURE into the VEINS.Cyclophosphamide: 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.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.Niacinamide: 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.Etoposide: 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.Vindesine: 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).Ifosfamide: Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.DNA Modification Methylases: 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.Organophosphorus Compounds: 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.Survival Rate: 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.Melanoma, Experimental: Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.Kaplan-Meier Estimate: 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)Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.GuanineRemission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level.Disease Progression: 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.Pheochromocytoma: 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)

Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age<...Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age<...
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 ...
Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells<...Inhibition of STAT3 reverses drug resistance acquired in temozolomide-resistant human glioma cells<...
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, ...
Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme - Full Text View -...Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme - Full Text View -...
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 ...
Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma | Molecular Cancer ResearchAugmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma | Molecular Cancer Research
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 ...
Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma | Molecular Cancer ResearchAugmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma | Molecular Cancer Research
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 ...
Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate...Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate...
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, ...
Clinical Study Phase II of L19IL2 in Combination With Dacarbazine in Patients With Metastatic Melanoma - Tabular View -...Clinical Study Phase II of L19IL2 in Combination With Dacarbazine in Patients With Metastatic Melanoma - Tabular View -...
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 ...
Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma. - The Christie...Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma. - The Christie...
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 ...
A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma<...A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma<...
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 ...
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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? - ASH Clinical NewsBrentuximab Vedotin Plus Dacarbazine or Bendamustine: New Options for Older Patients with Hodgkin Lymphoma? - ASH Clinical News
Brentuximab Vedotin Plus Dacarbazine or Bendamustine: New Options for Older Patients with Hodgkin Lymphoma? - Meeting News, Special Edition - ASH Clinical News
Final results of the TEMAVIR ANOCEF study in patients with unresectable glioblastoma | ESMOFinal results of the TEMAVIR ANOCEF study in patients with unresectable glioblastoma | ESMO
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. ...
Resveratrol abrogates the Temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the Temozolomide-induced...Resveratrol abrogates the Temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the Temozolomide-induced...
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 ...
Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in...Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in...
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...A Randomized, Placebo Controlled Phase IIb/III Study of ABT-414 with Concurrent Chemoradiation and Adjuvant Temozolomide in...
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)
Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma | HKMJFeasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma | HKMJ
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 ...
An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo for Newly Diagnosed...An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo for Newly Diagnosed...
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...Rare Cancer News & Clinical Trials » Trial - CNS Tumor » An Investigational Immuno-therapy Study of Temozolomide Plus Radiation...
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 ...
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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 ...
Augmented HR repair mediates acquired temozolomide resistance in glioblastoma - Fingerprint - University of Texas...Augmented HR repair mediates acquired temozolomide resistance in glioblastoma - Fingerprint - University of Texas...
Fingerprint Dive into the research topics of Augmented HR repair mediates acquired temozolomide resistance in glioblastoma. Together they form a unique fingerprint. ...
Efficacy of Novel Compound in Temozolomide-Resistant Brain Tumor Cell Lines in Mice | Penn State Hershey Neuro ReportEfficacy of Novel Compound in Temozolomide-Resistant Brain Tumor Cell Lines in Mice | Penn State Hershey Neuro Report
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 : usage, side effects, expert advice and temozolomide based medicines | 1mgTemozolomide : usage, side effects, expert advice and temozolomide based medicines | 1mg
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
Epigenetic characterisation of the 06 methyl-guanine DNA-methyltransferase promoter in New Zealand melanoma cell lines : a...Epigenetic characterisation of the 06 methyl-guanine DNA-methyltransferase promoter in New Zealand melanoma cell lines : a...
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 Portion of Trial of Dasatinib (Sprycel) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients...Phase II Portion of Trial of Dasatinib (Sprycel) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients...
Phase II: Primary Objectives: -To determine the effectiveness of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ)
Dacarbazine | Chemotherapy drugs - Macmillan Cancer SupportDacarbazine | Chemotherapy drugs - Macmillan Cancer Support
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.
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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, ...
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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 ...
Dacarbazine | Harvard Catalyst Profiles | Harvard CatalystDacarbazine | Harvard Catalyst Profiles | Harvard Catalyst
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 ...
Dacarbazine Side EffectsDacarbazine Side Effects
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.
Dr. George Demetri on the Mutagenic Properties and Future Potentials of DacarbazineDr. George Demetri on the Mutagenic Properties and Future Potentials of Dacarbazine
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.
Dacarbazine DosageDacarbazine Dosage
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.
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...
OncoLink, the Webs first cancer resource,provides comprehensive information on coping with cancer, cancer treatments, cancer research advances, continuing medical education, cancer prevention, and clinical trials
Survival Benefits of Front-Line Treatment With Nivolumab for Advanced Melanoma Confirmed, Yet Questions Remain - The ASCO PostSurvival Benefits of Front-Line Treatment With Nivolumab for Advanced Melanoma Confirmed, Yet Questions Remain - The ASCO Post
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 ...
Drug approved as part of frontline therapy for HL | MDedge Hematology and OncologyDrug approved as part of frontline therapy for HL | MDedge Hematology and Oncology
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. ...
Clinical Trial | Radiation Therapy or Radiation Therapy and Temozolomide or Temozolomide Alone in Treating Patients With Newly...Clinical Trial | Radiation Therapy or Radiation Therapy and Temozolomide or Temozolomide Alone in Treating Patients With Newly...
Radiation Therapy or Radiation Therapy and Temozolomide or Temozolomide Alone in Treating Patients With Newly Diagnosed Anaplastic Glioma This study is…
DACLIZUMAb, Dacarbazine, DACARBAZINE, Dabrafenib, Dabigatran, D4T, Online Medical Diagnosis and Drugs CatalogDACLIZUMAb, Dacarbazine, DACARBAZINE, Dabrafenib, Dabigatran, D4T, Online Medical Diagnosis and Drugs Catalog
DACLIZUMAb, Dacarbazine, DACARBAZINE, Dabrafenib, Dabigatran, D4T, Online Electronic Medical Diagnosis and Drugs, Medications, Articles, Glossary
Institute of Cancer Research Repository - A Phase I/II study of lomustine and temozolomide in patients with cerebral...Institute of Cancer Research Repository - A Phase I/II study of lomustine and temozolomide in patients with cerebral...
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 ...
Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report |...Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report |...
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 ...
18th World Congress of Basic and Clinical Pharmacology18th World Congress of Basic and Clinical Pharmacology
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 ...
A single cycle of treatment with temozolomide, alone or combined with O6-benzylguanine, induces strong chemoresistance in...A single cycle of treatment with temozolomide, alone or combined with O6-benzylguanine, induces strong chemoresistance in...
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 ...
ANAVEX 7-1037 Reduces Rate of Cancer Tumor Growth 69% in Pre-Clinical Studies, Compared to Currently Marketed Drug Dacarbazine...ANAVEX 7-1037 Reduces Rate of Cancer Tumor Growth 69% in Pre-Clinical Studies, Compared to Currently Marketed Drug Dacarbazine...
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 ...
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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 ...
Targeting the Akt-pathway to improve radiosensitivity in glioblastomaTargeting the Akt-pathway to improve radiosensitivity in glioblastoma
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 …
5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (dtic, Dic, nsc- - by S K. Carter and M A. Friedman"5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (dtic, Dic, nsc- -" by S K. Carter and M A. Friedman
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 ...
Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide.Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide.
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
Clinical trials of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) given intravenously in the treatment of...Clinical trials of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) given intravenously in the treatment 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 - ...
Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma...Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma...
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 ...
Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. - PubMed - NCBIRole of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. - PubMed - NCBI
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Radiation Therapy and Temozolomide Followed by Temozolomide and Poly ICLC in Treating Patients With Newly Diagnosed...Radiation Therapy and Temozolomide Followed by Temozolomide and Poly ICLC in Treating Patients With Newly Diagnosed...
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
Plus itPlus it
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 ...
Menin represses malignant phenotypes of melanoma through regulating multiple pathways - Gao - 2011 - Journal of Cellular and...Menin represses malignant phenotypes of melanoma through regulating multiple pathways - Gao - 2011 - Journal of Cellular and...
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. ...
A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma-First report of the full...A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma-First report of the full...
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 ...
GBM Treatment: One Small Step at a Time - Green Bay OncologyGBM Treatment: One Small Step at a Time - Green Bay Oncology
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 ...
Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or...Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or...
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 Aesarâ„¢ 2-Bromo-1-(cyanomethyl)imidazole-4,5-dicarbonitrile, 97% 250mg Alfa Aesarâ„¢ 2-Bromo-1-(cyanomethyl)imidazole-4,5...Alfa Aesarâ„¢ 2-Bromo-1-(cyanomethyl)imidazole-4,5-dicarbonitrile, 97% 250mg Alfa Aesarâ„¢ 2-Bromo-1-(cyanomethyl)imidazole-4,5...
Alfa Aesar™ 2-Bromo-1-(cyanomethyl)imidazole-4,5-dicarbonitrile, 97% 250mg Alfa Aesar™ 2-Bromo-1-(cyanomethyl)imidazole-4,5-dicarbonitrile, 97%...
Long-Term Data Show Optune Offers a Survival Benefit in GlioblastomaLong-Term Data Show Optune Offers a Survival Benefit in Glioblastoma
Long-term data from the phase 3 EF-14 study showed that Optune plus temozolomide had a survival benefit compared to temozolomide alone.
Clinical Trial | RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant GliomaClinical Trial | RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma
RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma This study is ongoing, but not recruiting…
A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial...A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial...
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.
A Phase I Study of MK-4827 in Combination with Temozolomide in Patients with Advanced CancerA Phase I Study of MK-4827 in Combination with Temozolomide in Patients with Advanced Cancer
The goal of this clinical research study is to find the highest tolerable dose of the combination of MK-4827 and temozolomide that can be given to patients with advanced solid cancers. The effects of the study drugs at different dose levels and the safety of the study drugs will also be studied. You are also being asked to take part in optional procedures, which are described in a separate consent form.
Alliance A071102Alliance A071102
A Phase II/III Randomized Trial of Veliparib or Placebo in Combination with Adjuvant Temozolomide in Newly Diagnosed Glioblastoma with Mgmt Promoter Hypermethylation. ...
RTOG opens phase III radiotherapy trial for glioblastomas | Health ImagingRTOG opens phase III radiotherapy trial for glioblastomas | Health Imaging
The Radiation Therapy Oncology Group (RTOG) has opened a new phase III trial for patients with newly diagnosed glioblastoma to determine if the addition of bevacizumab improves patient outcomes, compared with the current standard-of-care therapy--concurrent chemoradiation and adjuvant temozolomide.
Mechanisms of patient response to Dabrafenib in Melanoma - EGA European Genome-Phenome ArchiveMechanisms of patient response to Dabrafenib in Melanoma - EGA European Genome-Phenome Archive
Samples will be from the BRF113683 (BREAK-3) study which is a Phase III Randomized, Open-label Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma (n=250 enrolled)•NGS [Agilent capture (Sanger V2 panel): 360 genes and 20 gene fusions; Illumina HiSEQ Sequencing]•CNV: [via NGS or Affy SNP 6.0 or Illumina Omni (TBD)]Bioinformatics: Analysis will be performed using core Sanger informatics pipelines similar to those previously described (Papaemmanuil E et al. (2013) Blood. 22:3616 -3627). Briefly, copy number analysis will be performed using the ASCAT algorithm, and base substitutions, small insertions and deletions using the CAVEMAN and Pindel algorithms, respectively. Statistical approaches including generalized linear models will be used to predict clinical variables such as maximum clinical response and duration of response using genetic data. Sanger and EBI to conduct analysis; ...
New Tx for Metastatic Melanoma: PLX4032: liveonearth - LiveJournalNew Tx for Metastatic Melanoma: PLX4032: liveonearth - LiveJournal
melanoma prognosis: good if caught before mets, poor after (9 mo survival) 9,000 pts/yr die of it in US drugs currently approved to tx metastatic melanoma: interleukin-2 and dacarbazine benefit less than 20% of pts experimental anticancer drug: PLX4032 developed by Plexxikon Inc. of Berkeley…
Novel Agents Revolutionize Melanoma TreatmentNovel Agents Revolutionize Melanoma Treatment
Until recently, the cornerstone of therapy for metastatic melanoma had been chemotherapy with dacarbazine (DTIC) and immunotherapy with high-dose interleukin-2 (HD IL-2) or interferon-α (IFN-α).
Melanoma Drug Zelboraf Approved by FDA - Clinical ProfessionalsMelanoma Drug Zelboraf Approved by FDA - Clinical Professionals
The US Food and Drug Administration approved Roches Zelboraf yesterday for the treatment of patients with advanced melanoma that is beyond the reach of surgery.. Zelboraf (vemurafenib) was approved two months ahead of schedule by the FDA and is the second melanoma drug to be approved in 2011 after Bristol-Myers Squibbs Yervoy (ipilimumab), which debuted in March.. Both drugs have been hailed as a major advance in melanoma care, as they are the first new agents in over a decade to show any improvement in survival for patients with the disease. Roche and BMS are also working together to see if their two drugs can provide additional benefits when used in combination.. Zelborafs approval was supported by a single international trial of 675 previously-untreated patients with late-stage melanoma. Patients were assigned to receive either Zelboraf or dacarbazine and the median survival of those on Zelboraf has still not been reached, with 77% of patients still alive. For comparison, the median ...
NU1025 | CAS#90417-38-2 | PARP inhibitor | MedKoo BiosciencesNU1025 | CAS#90417-38-2 | PARP inhibitor | MedKoo Biosciences
NU1025 is a potent poly(ADP-ribose) polymerase (PARP) inhibitor, which potentiates the cytotoxicity of a panel of mechanistically diverse anti-cancer agents in L1210 cells. NU1025 enhanced the cytotoxicity of the DNA-methylating agent MTIC, gamma-irradiation and bleomycin 3.5-, 1.4- and 2-fold respectively.
Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems | OncotargetZinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems | Oncotarget
https://doi.org/10.18632/oncotarget.11382 Tatyana Pismenyuk, Michal Yalon, Shani Freedman, Amos J. Simon, Tamar Fisher, Itai Moshe, Juergen K.V. Reichardt, Shlomi Constantini, Yael Mardor, David...
TriazeneTriazene
ChemotherapyChemotherapy
Alkylating antineoplastic agentAlkylating antineoplastic agent
ABVDABVD
TemozolomideTemozolomide
Arabinopyranosyl-N-methyl-N-nitrosoureaArabinopyranosyl-N-methyl-N-nitrosourea
Budd-Chiari syndromeBudd-Chiari syndrome
FotemustineFotemustine
Adjuvant therapyAdjuvant therapy
Neuroblastoma RAS viral oncogene homologNeuroblastoma RAS viral oncogene homolog
Immune-Related Response CriteriaImmune-Related Response Criteria
VemurafenibVemurafenib
TremelimumabTremelimumab
DNA repairDNA repair
NeoplasmNeoplasm
SelumetinibSelumetinib
O-6-methylguanine-DNA methyltransferaseO-6-methylguanine-DNA methyltransferase
BinimetinibBinimetinib
SomatostatinomaSomatostatinoma
BRAF (gene)BRAF (gene)
EribulinEribulin
DoxorubicinDoxorubicin
TrabectedinTrabectedin
Brentuximab vedotinBrentuximab vedotin
List of MeSH codes (D03)List of MeSH codes (D03)
Nicholas ThatcherNicholas Thatcher
MEK inhibitorMEK inhibitor
ATC code L01ATC code L01
Chemotherapy-induced nausea and vomitingChemotherapy-induced nausea and vomiting
Gene signatureGene signature
DiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentInformation ScienceHealth Care
DacarbazineMelanomaVinblastineBleomycinMechlorethamineHodgkin DiseaseAntineoplastic Agents, AlkylatingProcarbazineAntineoplastic Combined Chemotherapy ProtocolsDoxorubicinSkin NeoplasmsVincristineNitrosourea CompoundsNimustineCarmustineMesnaLomustineInterferon-alphaCombined Modality TherapyPrednisoneO(6)-Methylguanine-DNA MethyltransferaseDisease-Free SurvivalTreatment OutcomeCisplatinChillsBenzenesulfonatesSurvival AnalysisHexanonesAntineoplastic AgentsTamoxifenNeoplasm MetastasisSarcomaAdministration, IntravenousCyclophosphamideDrug Administration ScheduleNeoplasm StagingPhenylurea CompoundsNiacinamideEtoposideVindesineIfosfamideDNA Modification MethylasesOrganophosphorus CompoundsSurvival RateMelanoma, ExperimentalKaplan-Meier EstimateInterleukin-2GuanineRemission InductionDisease ProgressionPheochromocytoma
Dacarbazine | Chemotherapy drugs - Macmillan Cancer SupportDacarbazine | Chemotherapy drugs - Macmillan Cancer Support
Dacarbazine | Harvard Catalyst Profiles | Harvard CatalystDacarbazine | Harvard Catalyst Profiles | Harvard Catalyst
Imatinib in Combination With Dacarbazine and Capecitabine in Medullary Thyroid Carcinoma - Tabular View - ClinicalTrials.govImatinib in Combination With Dacarbazine and Capecitabine in Medullary Thyroid Carcinoma - Tabular View - ClinicalTrials.gov
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...
Dr. George Demetri on the Mutagenic Properties and Future Potentials of DacarbazineDr. George Demetri on the Mutagenic Properties and Future Potentials of Dacarbazine
Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age<...Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age<...
Dacarbazine DosageDacarbazine Dosage
Dacarbazine Side EffectsDacarbazine Side Effects
Brentuximab Vedotin Plus Dacarbazine or Bendamustine: New Options for Older Patients with Hodgkin Lymphoma? - ASH Clinical NewsBrentuximab Vedotin Plus Dacarbazine or Bendamustine: New Options for Older Patients with Hodgkin Lymphoma? - ASH Clinical News
Injection Dacarbazine Supplier,Exporter,Wholesaler,Distributor,Manufacturer in IndiaInjection Dacarbazine Supplier,Exporter,Wholesaler,Distributor,Manufacturer in India
A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma<...A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma<...
Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate...Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate...
Dacarbazine - WikipediaDacarbazine - Wikipedia
Dacarbazine: MedlinePlus Drug InformationDacarbazine: MedlinePlus Drug Information
Dacarbazine News, ResearchDacarbazine News, Research
Dacarbazine Lyophilisate For Solution For Injection 100Mg Drug Medication Dosage InformationDacarbazine Lyophilisate For Solution For Injection 100Mg Drug Medication Dosage Information
Bevacizumab vs Dacarbazine in Metastatic Melanoma - Full Text View - ClinicalTrials.govBevacizumab vs Dacarbazine in Metastatic Melanoma - Full Text View - ClinicalTrials.gov
DBL Dacarbazine for Injection (Powder for injection) - myDr.com.auDBL Dacarbazine for Injection (Powder for injection) - myDr.com.au
Dacarbazine (DTIC, DIC, imidazole carboxamide) | Childrens Education MaterialsDacarbazine (DTIC, DIC, imidazole carboxamide) | Children's Education Materials
Ipilimumab plus dacarbazine for previously untreated metastatic melanomaIpilimumab plus dacarbazine for previously untreated metastatic melanoma
DBL Dacarbazine for Injection (Powder for injection)DBL Dacarbazine for Injection (Powder for injection)
Dacarbazine, DTIC injection - AHealthyMe - Blue Cross Blue Shield of MassachusettsDacarbazine, DTIC injection - AHealthyMe - Blue Cross Blue Shield of Massachusetts
Targeted Therapies Compared to Dacarbazine for Treatment of BRAFV600E Metastatic Melanoma: A Cost-Effectiveness AnalysisTargeted Therapies Compared to Dacarbazine for Treatment of BRAFV600E Metastatic Melanoma: A Cost-Effectiveness Analysis
Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma - Full Text View -...Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma - Full Text View -...
A Phase I/II Study of Sunitinib and DacarbazineA Phase I/II Study of Sunitinib and Dacarbazine
Dacarbazine (CAS 4342-03-4) Market Research Report 2018Dacarbazine (CAS 4342-03-4) Market Research Report 2018
Dacarbazine adverse effects - Answers on HealthTapDacarbazine adverse effects - Answers on HealthTap
Cabozantinib-S-Malate Compared With Temozolomide or Dacarbazine in Treating Patients With Metastatic Melanoma of the Eye That...Cabozantinib-S-Malate Compared With Temozolomide or Dacarbazine in Treating Patients With Metastatic Melanoma of the Eye That...
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...
Effects of interferon-[alpha], verapamil and dacarbazine in the treatment of advanced malignant melanomaEffects of interferon-[alpha], verapamil and dacarbazine in the treatment of advanced malignant melanoma
57-Early stage ABVD (DOXOrubicin bleomycin VinBLASTine dacarbazine) | eviQ57-Early stage ABVD (DOXOrubicin bleomycin VinBLASTine dacarbazine) | eviQ
PRIME PubMed | Reduction of Dacarbazine cytogenetic effects on somatic cells in male mice using bee glue (Propolis) to manifest...PRIME PubMed | Reduction of Dacarbazine cytogenetic effects on somatic cells in male mice using bee glue (Propolis) to manifest...
Abstract 2764: Effect of PNT2258 combinations with docetaxel, dacarbazine, or vemurafenib on the A375 melanoma xenograft |...Abstract 2764: Effect of PNT2258 combinations with docetaxel, dacarbazine, or vemurafenib on the A375 melanoma xenograft |...
A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of PARP in Combination With DacarbazineA Study to Assess the Safety and Pharmacokinetics of an Inhibitor of PARP in Combination With Dacarbazine
Dacarbazine toxicity in murine liver cells: a model of hepatic endothelial injury and glutathione defense. | Journal of...Dacarbazine toxicity in murine liver cells: a model of hepatic endothelial injury and glutathione defense. | Journal of...
Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkins lymphoma ...Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma ...
DiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentInformation ScienceHealth Care
DacarbazineMelanomaVinblastineBleomycinMechlorethamineHodgkin DiseaseAntineoplastic Agents, AlkylatingProcarbazineAntineoplastic Combined Chemotherapy ProtocolsDoxorubicinSkin NeoplasmsVincristineNitrosourea CompoundsNimustineCarmustineMesnaLomustineInterferon-alphaCombined Modality TherapyPrednisoneO(6)-Methylguanine-DNA MethyltransferaseDisease-Free SurvivalTreatment OutcomeCisplatinChillsBenzenesulfonatesSurvival AnalysisHexanonesAntineoplastic AgentsTamoxifenNeoplasm MetastasisSarcomaAdministration, IntravenousCyclophosphamideDrug Administration ScheduleNeoplasm StagingPhenylurea CompoundsNiacinamideEtoposideVindesineIfosfamideDNA Modification MethylasesOrganophosphorus CompoundsSurvival RateMelanoma, ExperimentalKaplan-Meier EstimateInterleukin-2GuanineRemission InductionDisease ProgressionPheochromocytoma
MelanomaChemotherapy1000 mgEffects of dacarbazineMetastaticIpilimumabLactate dehydrogenasePhaseDrugsBrentuximab vedotinDoseCombinationStudyPrevalentWeeksMetastatic melanomaDTIC-DomePlus dacarbazineVersus DacarbazineMalignant MelanomaVialDocetaxelImidazole carboxamideMechanism of actIntravenousSingle agent dacarbazineCarboxamideTreatmentCisplatinShown that dacarbazineAddition of dacarbazineHodgkin'sToxicityABVDHepaticGiven dacarbazineInclude dacarbazineReceive dacarbazineIngredientsRegimenTrabectedinIntravenouslyAbstractAllergicSupplierChemotherapeuticChemotherapy drugImpurityMelanoma therapyBelongs to the groupBody'sHospiraAntineoplastic
Melanoma2
Chemotherapy1
1000 mg1
Effects of dacarbazine2
Metastatic1
  • 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)
Ipilimumab1
Lactate dehydrogenase1
  • We conclude that dacarbazine is genotoxic and cytotoxic to the mouse testis in a transient fashion, and these effects are exerted along with decrease in testosterone and increase in lactate dehydrogenase levels in the testis. (elsevier.com)
Phase3
Drugs2
Brentuximab vedotin4
Dose2
  • Dacarbazine induced both head and tail abnormalities and some sperms with cytoplasmic droplets, but significant increase was seen in all dose groups on days 14 and 21, and at 100 mg/kg dose-level on day 35. (elsevier.com)
  • There was no particular dose-response of dacarbazine on any parameters tested. (elsevier.com)
Combination1
Study2
  • 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 first group of study participants will receive lower doses of imatinib mesylate, capecitabine and dacarbazine. (clinicaltrials.gov)
Prevalent1
Weeks1
  • 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. (elsevier.com)
Metastatic melanoma15
DTIC-Dome1
Plus dacarbazine10
Versus Dacarbazine3
Malignant Melanoma7
Vial3
Docetaxel1
  • 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)
Imidazole carboxamide1
Mechanism of act1
  • 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)
Intravenous3
Single agent dacarbazine2
Carboxamide3
  • 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)
Treatment23
Cisplatin5
  • This study presents data indicating that nanomolar concentrations of the hormonally active form of vitamin D, 1α,25‑dihydroxyvitamin D3 [1α,25(OH)2D 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)
Shown that dacarbazine1
Addition of dacarbazine3
Hodgkin's4
  • Dacarbazine was proven to be just as efficacious as procarbazine in the German trial for paediatric Hodgkin's lymphoma, without the teratogenic effects. (wikipedia.org)
  • When dacarbazine is used to treat Hodgkin's lymphoma is may be injected once a day for 5 days in a row every 4 weeks or it may be injected once every 15 days. (medlineplus.gov)
  • The usual recommended dosage of dacarbazine for treating Hodgkin's disease is 150 mg per m 2 daily for 5 days. (emedtv.com)
  • When used to treat Hodgkin's lymphoma, dacarbazine is used in combination with other medicines, regardless of the amount used. (emedtv.com)
Toxicity9
ABVD1
  • Interpretation: Dacarbazine cannot be omitted from ABVD without a substantial loss of efficacy. (mdc-berlin.de)
Hepatic1
  • 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)
Given dacarbazine2
  • 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)
Include dacarbazine1
Receive dacarbazine2
Ingredients4
Regimen3
Trabectedin1
Intravenously2
Abstract1
  • 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)
Allergic1
  • Tell your doctor if you have ever had any unusual or allergic reaction to dacarbazine or any other medicines. (drugster.info)
Supplier1
  • 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)
Chemotherapeutic2
Chemotherapy drug3
Impurity1
Melanoma therapy2
Belongs to the group1
Body's2
  • 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)
Hospira3
  • 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)
Antineoplastic2