Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.Radiation-Protective Agents: Drugs used to protect against ionizing radiation. They are usually of interest for use in radiation therapy but have been considered for other, e.g. military, purposes.MercaptoethylaminesXerostomia: Decreased salivary flow.Radiation Injuries: Harmful effects of non-experimental exposure to ionizing or non-ionizing radiation in VERTEBRATES.Radiation Injuries, Experimental: Experimentally produced harmful effects of ionizing or non-ionizing RADIATION in CHORDATA animals.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Testicular Diseases: Pathological processes of the TESTIS.Microradiography: Production of a radiographic image of a small or very thin object on fine-grained photographic film under conditions which permit subsequent microscopic examination or enlargement of the radiograph at linear magnifications of up to several hundred and with a resolution approaching the resolving power of the photographic emulsion (about 1000 lines per millimeter).Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.Samarium: Samarium. An element of the rare earth family of metals. It has the atomic symbol Sm, atomic number 62, and atomic weight 150.36. The oxide is used in the control rods of some nuclear reactors.Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy.Community Pharmacy Services: Total pharmaceutical services provided to the public through community pharmacies.Carcinoma, Non-Small-Cell Lung: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.Lung Neoplasms: Tumors or cancer of the LUNG.Universal Precautions: Prudent standard preventive measures to be taken by professional and other health personnel in contact with persons afflicted with a communicable disease, to avoid contracting the disease by contagion or infection. Precautions are especially applicable in the diagnosis and care of AIDS patients.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage.Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence.Cancer Care Facilities: Institutions specializing in the care of cancer patients.Medication Adherence: Voluntary cooperation of the patient in taking drugs or medicine as prescribed. This includes timing, dosage, and frequency.Access to Information: Individual's rights to obtain and use information collected or generated by others.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Peer Review, Research: The evaluation by experts of the quality and pertinence of research or research proposals of other experts in the same field. Peer review is used by editors in deciding which submissions warrant publication, by granting agencies to determine which proposals should be funded, and by academic institutions in tenure decisions.Ophthalmoplegia, Chronic Progressive External: A mitochondrial myopathy characterized by slowly progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. Ragged-red fibers and atrophy are found on muscle biopsy. Familial and sporadic forms may occur. Disease onset is usually in the first or second decade of life, and the illness slowly progresses until usually all ocular motility is lost. (From Adams et al., Principles of Neurology, 6th ed, p1422)Saliva: The clear, viscous fluid secreted by the SALIVARY GLANDS and mucous glands of the mouth. It contains MUCINS, water, organic salts, and ptylin.Survivors: Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events.Randomized Controlled Trials as Topic: Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table.Consensus Development Conferences, NIH as Topic: Articles on conferences sponsored by NIH presenting summary statements representing the majority agreement of physicians, scientists, and other professionals convening for the purpose of reaching a consensus on a subject of interest. This heading is used for NIH consensus conferences as a means of scientific communication. In indexing it is viewed as a type of review article and as a tag for any article appearing in any publication of the NIH Office of Medical Applications of Research (OMAR).Consensus Development ConferenceConsensus Development Conference, NIHResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.Stomatitis: INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP.Nova Scotia: A province of eastern Canada, one of the Maritime Provinces with NEW BRUNSWICK; PRINCE EDWARD ISLAND; and sometimes NEWFOUNDLAND AND LABRADOR. Its capital is Halifax. The territory was granted in 1621 by James I to the Scotsman Sir William Alexander and was called Nova Scotia, the Latin for New Scotland. The territory had earlier belonged to the French, under the name of Acadia. (From Webster's New Geographical Dictionary, 1988, p871 & Room, Brewer's Dictionary of Names, 1992, p384)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.Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.Paclitaxel: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.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)Mesothelioma: A tumor derived from mesothelial tissue (peritoneum, pleura, pericardium). It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. (Dorland, 27th ed)Pleural Neoplasms: Neoplasms of the thin serous membrane that envelopes the lungs and lines the thoracic cavity. Pleural neoplasms are exceedingly rare and are usually not diagnosed until they are advanced because in the early stages they produce no symptoms.Pneumonectomy: The excision of lung tissue including partial or total lung lobectomy.Thoracic Cavity: The region of the thorax that includes the PLEURAL CAVITY and MEDIASTINUM.Neoplasm Recurrence, Local: The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.Amyloidosis: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.Mucinoses: Mucoid states characterized by the elevated deposition and accumulation of mucin (mucopolysaccharides) in dermal tissue. The fibroblasts are responsible for the production of acid mucopolysaccharides (GLYCOSAMINOGLYCANS) in the ground substance of the connective tissue system. When fibroblasts produce abnormally large quantities of mucopolysaccharides as hyaluronic acid, chondroitin sulfate, or heparin, they accumulate in large amounts in the dermis.Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.Amyloidosis, Familial: Diseases in which there is a familial pattern of AMYLOIDOSIS.Paraproteinemias: A group of related diseases characterized by an unbalanced or disproportionate proliferation of immunoglobulin-producing cells, usually from a single clone. These cells frequently secrete a structurally homogeneous immunoglobulin (M-component) and/or an abnormal immunoglobulin.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.

Evaluation of uroprotective efficacy of amifostine against cyclophosphamide induced hemorrhagic cystitis. (1/192)

The role of amifostine in the prevention of cyclophosphamide-induced hemorrhagic cystitis (HC) was evaluated in the rat model. Urinary bladders from control rats that received no drugs (group I) were compared with those from rats receiving cyclophosphamide alone at a dose of 150 mg/kg (group II), and two other groups receiving amifostine at 100 mg/kg (group III) and 200 mg/kg (group IV), 15 min prior to cyclophosphamide. Bladders were assessed macroscopically and histologically at 24 h and after 7 days. All the animals that received cyclophosphamide alone developed severe HC. On the basis of the scores of macroscopic and histologic changes, animals that received amifostine showed excellent uroprotection. Only 2/6 rats in group III and 1/6 rats in group IV developed mild HC at 24 h. None of the rats in either of these groups showed any evidence of HC at 7 days. It is concluded that amifostine protects the urothelium against cyclophosphamide-induced HC.  (+info)

The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects. (2/192)

Radio- and chemotherapy for the treatment of malignancies are often associated with significant toxicity. One approach to reduce the toxicity is the concomitant treatment with chemoprotective agents. This article reviews two sulfhydryl compounds, namely the agent WR-2721 (amifostine), a compound recently registered for use in human in many countries, and the natural occurring compound glutathione (GSH). GSH is not registered as a chemoprotective agent. WR-2721 is an aminothiol prodrug and has to be converted to the active compound WR-1065 by membrane-bound alkaline phosphatase. WR-1065 and GSH both act as naturally occurring thiols. No protective effect on the tumour has been found when these compounds are administered intravenously. There is even in vitro evidence for an increased anti-tumour effect with mafosfamide after pretreatment with WR-2721, and in vivo after treatment with carboplatin and paclitaxel. Randomized clinical studies have shown that WR-2721 and GSH decrease cisplatin-induced nephrotoxicity and that WR-2721 reduces radiation radiotherapy-induced toxicity. Side-effects associated with WR-2721 are nausea, vomiting and hypotension, GSH has no side-effects. An exact role of WR-2721 and GSH as chemoprotectors is not yet completely clear. Future studies should examine the protective effect of these drugs on mucositis, cardiac toxicity, neuro- and ototoxicity, the development of secondary neoplasms and their effect on quality of life.  (+info)

Direct amifostine effect on renal tubule cells in rats. (3/192)

Clinical trials indicate that amifostine offers protection against cisplatin-induced nephrotoxicity. It is unclear whether a direct pharmacological t on renal tubular cells is involved. We investigated the effect of amifostine pretreatment on the tubular apparatus and evaluated its nephroprotective potential. A total of 32 rats were treated by i.p. administration of 0.9% saline solution (group 1), 5 mg/kg cisplatin (group 2), 25 mg/kg amifostine (group 3), and 25 mg/kg amifostine followed by 5 mg/kg cisplatin (group 4) after 30 min. We recorded elevation of N-acetyl-beta-D-glucosaminidase (NAG) in 24 h pooled urine as a specific marker for tubular lesions, renal leakage of magnesium as an unspecific nephrotoxicity marker, and survival over a 10-day observation period. A significant (P < 0.002) increase in urinary NAG after treatment was documented only in cisplatin-treated group 2 [day 2 (mean+/-SE), 93+/-2.1 units/gram creatinine; day 4, 70.6+/-16 units/gram creatinine; normalization at day 8]. Treatment with amifostine before cisplatin administration resulted in a slight urinary NAG leakage (day 2, 2.8+/-1.8 units/gram creatinine; day 4, 13.8+/-13 units/gram creatinine; normalization at day 6). No increase in urinary enzyme levels was seen in the other groups, and there were no significant differences in urinary magnesium between all groups. Four of eight rats in the cisplatin-treated group and one of eight rats in the amifostine plus cisplatin-treated group died.  (+info)

Randomized study of a short course of weekly cisplatin with or without amifostine in advanced head and neck cancer. EORTC Head and Neck Cooperative Group. (4/192)

BACKGROUND: Cisplatin is one of the most active cytotoxic agents available for the treatment of patients with head and neck cancer. In a previous phase II study with weekly administration of cisplatin, a response rate of 51% was achieved. However, only in a minority of the patients the planned high dose intensity of 80 mg/m2/week could be reached because of toxicity, mainly thrombocytopenia and ototoxicity. Amifostine is a cytoprotective drug that can diminish the toxicity of alkylating agents and platinum compounds. Therefore the effect of amifostine on toxicity and activity of weekly cisplatin was investigated in a randomized study. PATIENTS AND METHODS: Patients with locally advanced, recurrent or metastatic head and neck cancer were eligible. Patients were randomized to weekly cisplatin 70 mg/m2 for six cycles preceded by amifostine 740 mg/m2, or cisplatin only. Cisplatin was administered in hypertonic saline (3% NaCl) as a one-hour infusion; amifostine was administered as a 15-minute infusion directly before the administration of cisplatin. RESULTS: Seventy-four patients were entered in the study. The median number of cisplatin administrations was 6 (range 2-6), equal in both arms. In both treatment arms the median dose intensity of cisplatin achieved was the planned 70 mg/m2/week. In the cisplatin only arm 6 out of 206 cycles were complicated by thrombocytopenia grade 3 or 4 versus 1 of 184 cycles in the amifostine arm (P = 0.035). Hypomagnesaemia grade 2 + 3 was significantly less observed in the amifostine arm (P = 0.04). Neurotoxicity analyzed by serial vibration perception thresholds (VPT) showed a diminished incidence of subclinical neurotoxicity in the amifostine arm (P = 0.03). No protective effect on renal and ototoxicity could be shown. Hypotension was the main side effect of amifostine but only of relevance in one patient. The antitumor activity of cisplatin was preserved as 63% of the evaluable patients in the amifostine arm responded compared to 50% of the evaluable patients in the cisplatin alone arm. CONCLUSION: Our study indicated that in combination with weekly administered cisplatin amifostine reduced the risk of thrombocytopenia, hypomagnesemia as well as subclinical neurotoxicity, but did not result in a higher dose intensity of cisplatin. Addition of amifostine did not compromise the antitumor effect of cisplatin.  (+info)

Randomized phase II study of high-dose paclitaxel with or without amifostine in patients with metastatic breast cancer. (5/192)

PURPOSE: To determine whether the neurotoxicity of paclitaxel 250 mg/m(2) given over 3 hours every 3 weeks could be reduced by pretreatment with amifostine 910 mg/m(2). Secondary objectives included comparing myelosuppression, myalgias, and response rates of the two groups. PATIENTS AND METHODS: Forty women with metastatic breast cancer were randomized to receive either paclitaxel alone (arm 1) or paclitaxel preceded by amifostine (arm 2). All were assessable for toxicity, and 37 were assessable for response. At baseline and after each cycle, all patients completed questionnaires for neurologic symptoms and had standardized neurologic examinations, including objective assessments of power and vibration sense. In addition, standard follow-up assessments for other toxicities and tumor response were undertaken. Changes from baseline after courses 1, 2, and 3 were assessed. The sample size was sufficient to detect a 50% improvement in the expected determination in sensory change. RESULTS: There were no differences observed in any of the measures of neurotoxicity. Other toxicity was similar in arms 1 and 2, including hair loss (95% v 90%), neurosensory changes (100% v 100%), fatigue/lethargy (85% v 90%), myalgia (95% v 90%), and grade 4 neutropenia (47% v 60%). Nausea, vomiting, dizziness, hypotension, and sneezing were more common in the amifostine arm. Response rates (22.2% v 36.8%) and paclitaxel pharmacokinetics were not significantly different. CONCLUSION: There was no protection from paclitaxel-related neurotoxicity or hematologic toxicity in this study. These results suggest that the mechanism of action of paclitaxel-related toxic effects is not amenable to the cytoprotective action of amifostine.  (+info)

American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. (6/192)

PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth  (+info)

The potential of amifostine: from cytoprotectant to therapeutic agent. (7/192)

BACKGROUND AND OBJECTIVE: Amifostine is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[(3-aminopropyl)amino]dihydrogen phosphate. It is a pro-drug of free thiol that may act as a scavenger of free radicals generated in tissues exposed to cytotoxic drugs, and binds to reactive metabolites of such drugs. Amifostine was originally developed as a radioprotective agent in a classified nuclear warfare project. Following declassification of the project it was evaluated as a cytoprotective agent against toxicity of the alkylating drugs and cisplatin. In fact, pretreatment with amifostine was well tolerated and reduced the cumulative hematologic, renal and neurological toxicity associated with cisplatin, cyclophosphamide and vinblastine therapy of advanced and metastatic solid tumors. The objective of this review is to focus the importance of amifostine as a myeloprotective and cytoprotective drug during treatment with chemotherapeutics, presenting the most recent results, and to discuss the application of amifostine in the therapy of myelodysplastic syndromes. EVIDENCE AND INFORMATION SOURCES: The material analyzed in this study includes data published or under publication by the authors as full papers or clinical protocols. Articles and abstracts published in Journals covered by Medline constitute the other source of information. STATE OF THE ART AND PERSPECTIVES: Amifostine, formerly known as WR-2721, is an organic thiophosphate that was developed to protect normal tissues selectively against the toxicities of chemotherapy and radiation. Amifostine is a pro-drug that is dephosphorylated at the tissue site to its active metabolite by alkaline phosphatase. Differences in the alkaline phosphatase concentrations of normal versus tumor tissues can result in greater conversion of amifostine in normal tissues. Once inside the cell the free thiol provides an alternative target to DNA and RNA for the reactive molecules of alkylating or platinum agents and acts as a potent scavenger of the oxygen free radicals induced by ionizing radiation and some chemotherapies. Preclinical animal studies demonstrated that the administration of amifostine protected against a variety of chemotherapy-related toxicities including cisplatin-induced nephrotoxicity, cisplatin-induced neurotoxicity, cyclophosphamide- and bleomycin-induced pulmonary toxicity, and the cytotoxicities (including cardiotoxicity) induced by doxorubicin and related chemotherapeutic agents. Amifostine was shown to protect a variety of animal species from lethal doses of radiation. Studies in tumor-bearing animals demonstrated that the administration of amifostine results in cytoprotection without loss of antitumor activity. Multiple phase I studies were carried out with amifostine in combination with chemotherapy for various neoplasms. Appropriate doses of amifostine resulted to be 740-910 mg/m(2) in a single dose regimen, and 340 mg/m(2) in a multiple dose regimen. Amifostine afforded not only hematologic protection, but also other organ protection from cytotoxic agents such as nephrotoxicity, mucositis and peripheral neuropathy from cisplatin. Many studies have been performed to investigate cytoprotective efficacy of amifostine. In brief, amifostine gives hematologic protection from cyclophosphamide, carboplatin, mitomycin C, fotemustine and radiotherapy; renal and peripheral nerve protection from cisplatin; mucosa, skin, and salivary gland from radiotherapy. In phase I/II studies these properties have been confirmed, together with a generally good tolerability of the drug, hypotension being the most common side effect. It has been observed that amifostine possibly enhances the anti-tumor effect of carboplatin, nitrogen mustard, melphalan, and cisplatin combined with 5-FU or vinblastine. For all these characteristics, amifostine is at present broadly used as supportive treatment during chemotherapy, in lymphomas and solid tumors, and its spec  (+info)

Amifostine inhibits hematopoietic progenitor cell apoptosis by activating NF-kappaB/Rel transcription factors. (8/192)

We investigated the involvement of NF-kappaB/Rel transcription factors that reportedly can inhibit apoptosis in various cell types in the antiapoptotic mechanism of the cytoprotectant amifostine. In the nontumorigenic murine myeloid progenitor 32D cells incubated with amifostine, we detected a reduction of the IkappaBalpha cytoplasmic levels by Western blotting and a raising of nuclear NF-kappaB/Rel complexes by electrophoretic mobility shift assay. Amifostine inhibited by more than 30% the growth factor deprivation-induced apoptosis, whereas its effect failed when we blocked the NF-kappaB/Rel activity with an NF-kappaB/Rel-binding phosphorothioate decoy oligodeoxynucleotide. In human cord blood CD34(+) cells, the NF-kappaB/Rel p65 subunit was detectable (using immunofluorescence analysis) mainly in the cytoplasm in the absence of amifostine, whereas its presence was appreciable in the nuclei of cells incubated with the cytoprotectant. In 4 CD34(+) samples incubated for 3 days in cytokine-deficient conditions, cell apoptosis was reduced by more than 30% in the presence of amifostine (or amifostine plus a control oligo); the effect of amifostine was abolished in cultures with the decoy oligo. These findings indicate that the inhibition of hematopoietic progenitor cell apoptosis by amifostine requires the induction of NF-kappaB/Rel factors and that the latter can therefore exert an antiapoptotic activity in the hematopoietic progenitor cell compartment. Furthermore, the identification of this specific mechanism underlying the survival-promoting activity of amifostine lends support to the possible use of this agent in apoptosis-related pathologies, such as myelodysplasias.  (+info)

  • Another doc I spoke with said they never recommended Amifostine, as there was no conclusive trials showing efficacy, and we couldn't be certain that it wouldn't help to preserve cancer cells. (cancer.org)
  • This trial tested the hypothesis that SbQ amifostine was associated with an improved toxicity profile with regards to late xerostomia versus IV amifostine. (oncolink.org)
  • There are several advantages offered by SbQ amifostine over IV amifostine including easier administration and a favorable window between drug injection and radiation delivery. (oncolink.org)
  • Constantly increasing inpatient admission of patients suffering from cancer and Availability of Amifostine Hydrate injection at a low cost in the government-funded hospitals and clinics determine its market growth. (fnbherald.com)
  • Amifostine works by selectively protecting normal but not tumor tissues from cytotoxic effects of radiation therapy and chemotherapy. (ons.org)
  • The primary endpoint was the proportion of 5-FU/calcium folinate doses associated with diarrhea or amifostine toxicity. (ons.org)
  • 0.04) was found in the mean number of administered doses of 5-FU between patients before and after treatment with amifostine. (ons.org)
  • No significant difference was found between mean 5-FU doses during treatment with amifostine. (ons.org)
  • Although previous studies have found that doses of amifostine between 740-910 mg/m 2 are effective, this study suggested that lower doses may be effective and increase tolerability. (ons.org)
  • Amifostine appears to offer protection against gastrointestinal adverse effects and permit higher doses of 5-FU. (ons.org)
  • Pharmaceutical companies manufacturing Amifostine Hydrate injections are Cumberland Pharmaceuticals, Mylan Labs Ltd., CSC Pharmaceuticals International, Natco Pharma Limited, Clinigen Group, Sun Pharmaceutical Industries Ltd., Taj Pharmaceuticals Limited, Merro Pharmaceutical Co., Ltd. Luye Pharma Group and Mingren Pharma. (fnbherald.com)
  • During my rads treatment I took two shots before they zapped my head called amifostine. (cancer.org)
  • It is recommended that antiemetic medication, including dexamethasone 20 mg intravenously and a serotonin 5-HT3 receptor antagonist, be administered prior to and in conjunction with amifostine. (drugs.com)
  • It is recommended that antiemetic medication be administered prior to and in conjunction with amifostine. (drugs.com)
  • Group I (n = 18) received 800 mg/m 2 amifostine weekly. (ons.org)
  • Group II (n = 16) received a lowered dose of 500 mg/m 2 amifostine weekly. (ons.org)
  • Group III (n = 18) received a lowered dose of 150 mg/m 2 amifostine weekly. (ons.org)
  • ETHYOL® (amifostine) is a prescription drug given by injection prior to each postoperative radiation treatment session for head and neck cancer. (cancer.org)
  • Cumberland markets branded amifostine in the U.S territory under the name Ethyol ® on behalf of Clinigen Group plc who is the market authorization holder and owner of global rights. (prnewswire.com)
  • We undertook a phase III randomized, multicenter trial to investigate whether daily pretreatment with amifostine (Ethyol) could safely reduce the incidence of esophagitis and pneumonitis in patients with lung cancer undergoing definitive conventional radiotherapy. (cancernetwork.com)
  • ETHYOL (amifostine) is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. (ethyol.com)
  • ETHYOL (amifostine) is a protective medicine. (ethyol.com)
  • Are taking a medicine called amifostine because it contains the same medicine as ETHYOL. (ethyol.com)
  • ETHYOL contains the same medicine as amifostine. (ethyol.com)
  • If you are taking amifostine, do not take ETHYOL. (ethyol.com)
  • Amifostine (Ethyol) may be considered to decrease the incidence of xerostomia in certain patients undergoing fractionated radiation therapy to the head and neck region. (aafp.org)
  • This week, the Advisor Forum answers a question about the use of amifostine (Ethyol, generic) as a radioprotectant. (oncologynurseadvisor.com)
  • Amifostine was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer. (wikipedia.org)
  • a U.S. specialty pharmaceutical company and Clinigen Group plc (AIM: CLIN, 'Clinigen') , the global pharmaceutical and services company, announce a new publication in Leukemia & Lymphoma , with study results showing that amifostine decreases gastro-intestinal (GI) toxicity in patients who receive treatment for their multiple myeloma. (prnewswire.com)
  • The study concluded that amifostine therapy decreased GI toxicity without any significant adverse effects while preserving the anti-myeloma efficacy of high-dose melphalan and auto-HTC. (prnewswire.com)
  • Amifostine is an organic thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or non-small cell lung cancer and also to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer. (drugbank.ca)
  • Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite, believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. (drugbank.ca)
  • Acute pulmonary toxicity was also significantly lower in the patients treated with amifostine. (cancernetwork.com)
  • Amifostine significantly reduced esophagitis, reduced late lung toxicity, reduced the clinical symptoms such as dyspnea and cough, and reduced the incidence of pneumonitis and fibrosis. (cancernetwork.com)
  • Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. (frontiersin.org)
  • OBJECTIVES: I. Assess the toxicity profile of irinotecan and amifostine when administered together in patients with metastatic colorectal cancer. (knowcancer.com)
  • This trial tested the hypothesis that SbQ amifostine was associated with an improved toxicity profile with regards to late xerostomia versus IV amifostine. (oncolink.org)
  • Amifostine induced a G1 arrest and protected against paclitaxel toxicity in p53-proficient but not in p53-deficient cells. (nih.gov)
  • Three well-controlled clinical trials have shown that amifostine can ameliorate cumulative bone marrow toxicity and the acute and chronic neutropenic and/or thrombocytopenic effects of cyclophosphamide. (elsevier.com)
  • Jan. 30, 2018 /PRNewswire/ -- Cumberland Pharmaceuticals Inc. (NASDAQ: CPIX) , a U.S. specialty pharmaceutical company and Clinigen Group plc (AIM: CLIN, ' Clinigen ') , the global pharmaceutical and services company, announce a new publication in Leukemia & Lymphoma , with study results showing that amifostine decreases gastro-intestinal (GI) toxicity in patients who receive treatment for their multiple myeloma. (gcs-web.com)
  • Amifostine is a unique drug selectively protecting non-affected tissues from CT-RT induced toxicity. (springer.com)
  • IMSEAR at SEARO: Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity. (who.int)
  • Gautam Anshoo, Gupta Alka, Lomash Vinay, Pant S C, Vijayaraghavan R. Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity. (who.int)
  • p53 protein regulates the effects of amifostine on apoptosis, cell cycle progression, and cytoprotection. (nih.gov)
  • These findings indicate that amifostine-induced G1 arrest and cytoprotection are mediated via a pathway that is dependent on p53 protein and that amifostine-induced expression of p21 protein is not sufficient to sustain a G1 arrest or to mediate cytoprotection. (nih.gov)
  • Its aim was to determine if the amifostine group experienced less weight loss, less use of opiates during treatment, and/or allowed for a higher dose of radiotherapy to be delivered before opioids were needed for symptomatic relief of acute esophagitis. (prnewswire.com)
  • After week 3 we observed a significant reduction in acute esophagitis in patients who received amifostine,' Dr. Antonadou said. (cancernetwork.com)
  • In this study, we have investigated the in vivo effects of IL-4, IL-10, and amifostine on cytokine production in patients with acute myelogenous leukemia (AML). (elsevier.com)
  • Amifostine is a cytoprotective compound that has been shown to protect against the acute cytotoxicities of anthracyclines in animal models. (elsevier.com)
  • Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury. (biomedcentral.com)
  • The aim of the present study was to evaluate antioxidative ability of amifostine in blood serum of rats exposed to cyclophosphamide during two weeks after drug administration. (pjoes.com)
  • The addition of amifostine does not allow dose escalation of idarubicin when combined with high-dose ara-C. (elsevier.com)
  • The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome. (springer.com)
  • Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A) (subcutaneously, 500 mg flat dose) before radiotherapy or radiotherapy alone (R). Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. (biomedcentral.com)
  • Amifostine is rapidly dephosphorylated by alkaline phosphatase in tissues primarily to the active free thiol metabolite and, subsequently, to a less active disulfide metabolite. (drugbank.ca)
  • This research study is studying a drug called Amifostine as a treatment for squamous cell carcinoma in the head and/or neck area. (clinicaltrials.gov)
  • Furthermore, CCM-Ami pretreatment improved survival rates and median survival in C57BL/6 mice than did treatment with a corresponding dose of amifostine. (omicsonline.org)
  • Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures. (who.int)
  • Amifostine comes as a powder to be mixed with liquid to be injected intravenously (into a vein) by a doctor or nurse in a medical facility. (medlineplus.gov)
  • Amifostine can be administered intravenously or subcutaneously after reconstitution with normal saline. (wikipedia.org)
  • It is recommended that antiemetic medication, including dexamethasone 20 mg intravenously and a serotonin 5-HT3 receptor antagonist, be administered prior to and in conjunction with amifostine. (drugs.com)
  • Amifostine is used to protect the kidneys from harmful effects caused by cisplatin when given to patients with ovarian cancer. (cigna.com)
  • Here you can see the latest Amifostine In Treating Women With Ovarian, Peritoneal, Cervical, Fallopian Tube, Uterine, Or Endometrial Cancer articles that have been published worldwide. (bioportfolio.com)
  • In addition to the medical data, news and clinical trials, BioPortfolio also has a large collection of Amifostine In Treating Women With Ovarian, Peritoneal, Cervical, Fallopian Tube, Uterine, Or Endometrial Cancer Companies in our database. (bioportfolio.com)
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  • The amount or dosage of Amifostine received by the patient depends on several factors such as the height and weight of the patient, the general health profile as well as the health condition that is being treated. (chemistrylearner.com)
  • Amifostine as a thiol compound possesses antioxidant properties and protects only healthy cells against damage, mainly by scavenging reactivity oxygen species, competing with oxygen to prevent oxygen radical interactions with DNA, and promoting cell repair through hydrogen donation to reactive oxygen species. (pjoes.com)
  • N-acetyl cysteine protects against DNA damage, suggested to be comparable to amifostine. (wikipedia.org)
  • Amifostine may also be used for purposes not listed in this medication guide. (cigna.com)
  • You will need to stop taking any blood pressure medication for at least 24 hours before you are treated with amifostine. (cigna.com)
  • To be sure this medication is not causing harmful effects, your blood pressure will be watched closely while you are receiving amifostine. (cigna.com)
  • It is recommended that antiemetic medication be administered prior to and in conjunction with amifostine. (drugs.com)
  • Additional data have shown that amifostine-mediated tumor protection, in any clinical scenario, is unlikely. (wikipedia.org)
  • You may be given other medications to prevent nausea or vomiting while you are receiving amifostine. (cigna.com)
  • Along with Amifostine, anti-nausea drug may also be administered to the patient. (chemistrylearner.com)
  • When used, amifostine (600 mg/m 2 /dose) was administered as a bolus immediately before and 3 hours into the cisplatin infusion. (elsevier.com)
  • ages 3-21 years), enrolled on one of 2 sequential St. Jude clinical protocols that included 4 courses of 75 mg/m(2) cisplatin, were compared for hearing loss by whether or not they received 600 mg/m(2) of amifostine immediately before and 3 hours into each cisplatin infusion. (duke.edu)
  • The preparation of amifostine-loaded CCM (CCM-Ami) was simply mixing ferrous chloride, poly(ethylene glycol)-block-poly (glutamic acid) (PEG-b-PGA) and amifostine in an aqueous solution without using any organic solvent. (omicsonline.org)
  • In this work, we developed a versatile dual-readout (colorimetric and fluorometric) amifostine (WR2721) sensor based on the inner filter effect (IFE) of gold nanoparticles (AuNPs) on sulfanilic acid functionalized graphene quantum dots (SGQDs). (rsc.org)
  • amifostine 'WR2721' the first selective-target and broad-spectrum radioprotector, upregulates DNA repair. (wikipedia.org)
  • Pharmaceutical companies manufacturing Amifostine Hydrate injections are Cumberland Pharmaceuticals, Mylan Labs Ltd., CSC Pharmaceuticals International, Natco Pharma Limited, Clinigen Group, Sun Pharmaceutical Industries Ltd., Taj Pharmaceuticals Limited, Merro Pharmaceutical Co., Ltd. Luye Pharma Group and Mingren Pharma. (curiousdesk.com)
  • Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. (bvsalud.org)