Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytoprotection utilising amifostine (Ethyol, WR-2721) is an evolving strategy to protect normal cells from the toxicity of chemotherapy. The dosing and administration guidelines are reviewed. The recommended dose of amifostine is 910 mg/m2 as a 15-min infusion prior to chemotherapy. Toxicity of this agent is moderate with hypotension and nausea/vomiting being observed in variable numbers of patients. Administration of amifostine with chemotherapy is simple and is associated with acceptable toxicity.
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PMID:Amifostine (Ethyol): dosing, administration and patient management guidelines. 897 23

The aminothiol, amifostine (Ethyol; U.S. Bioscience, West Conshohocken, PA), is a cytoprotective agent that ameliorates the toxicities of anticancer therapy. In vitro, amifostine promotes the formation and survival of primitive hematopoietic progenitors derived from myelodysplastic bone marrow (BM) specimens. To evaluate the hematological effects of amifostine, 18 patients with myelodysplastic syndrome (MDS) and one or more refractory cytopenias received treatment with amifostine in a Phase I/II study. Four cohorts received intravenous treatment with 100, 200, or 400 mg/m2 amifostine three times a week, or 740 mg/m2 weekly for three consecutive weeks followed by 2 weeks observation. Nonresponding patients received a second course of therapy at the next higher dose level depending upon drug tolerance. Bone marrow (BM) progenitor growth was assessed before treatment and after day 21. Diagnoses included refractory anemia (7), refractory anemia with ringed sideroblasts (5), refractory anemia with excess blasts (RAEB) (4), and RAEB-in transformation (RAEB-t) (2). Single- or multi-lineage hematologic responses occurred in 15 patients (83%) treated with the three-times-a-week dose schedule. Fourteen patients had a 50% or greater increase in absolute neutrophil count with amifostine treatment (range, 426 to 11,348/microL). Platelet count increased in 6 (43%) of 14 patients with thrombocytopenia (absolute increase, 16, 000 to 110,000/microL), and 5 of 15 red blood cell transfusion-dependent patients had a 50% of greater reduction in transfusion needs. Assayable hematopoietic progenitors increased in 13 of 15 evaluable patients; including CFU-GEMM (12), BFU-E (8), and CFU-GM (6). Amifostine doses less than or equal to 200 mg/m2 were well tolerated, whereas grade II nausea, vomiting, and fatigue was limiting at higher doses. Three patients with excess blasts before enrollment experienced an increase in BM blast percentage and two patients had evolution to acute leukemia that persisted after treatment withdrawal. We conclude that amifostine administered at doses </=200 mg/m2 three times a week is well tolerated and has hematologic activity in patients with MDS.
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PMID:Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome. 1153 40

Recent advances in chemotherapy have focused on the benefit of high dose regimens, increasing the dose intensity of conventional chemotherapy and using intensified chemotherapy with or without autologous bone marrow rescue. Dose intensity usually increases objective response rates of antineoplastic drugs and might, in some circumstances, improves survival. However, unacceptable acute and/or cumulative toxicity often impairs the proper management of patients, leading to dose reduction or treatment delay, thus reducing the efficacy and potentially the quality of life of patients. Therefore, considerable efforts have been made to manage, to prevent, and to delay many acute and cumulative treatment-related toxicities. Amifostine (WR-2721 ) is a multiorgan cytoprotector which has demonstrated cytoprotective effects, in vitro and in vivo, against the most common cytotoxic drug-related toxicities and against radiation-induced adverse effects in healthy tissues. In vitro and in vivo, cytoprotection was observed in several organs including kidney, haematopoietic stem cells, myocardial cells, neural cells, and mucosa, without detectable protection of malignant cells. In addition, in preclinical studies, amifostine appeared to be able to reduce the risk of radiation-induced secondary neoplasms. Phase I studies showed that nausea/vomiting and hypotension are the dose-limiting toxicities of amifostine and these may be controlled by reducing the duration of injection of amifostine. Phase II and randomised studies have confirmed the efficacy of amifostine in protecting against radiotherapy-induced mucositis, cisplatin-induced nephrotoxicity, cyclophosphamide-induced neutropenia and carboplatin-induced thrombocytopenia. Importantly, the cytoprotection of healthy tissues occurred without any significant deleterious effect on response rate, time to progression, and survival of patients receiving amifostine. However, in addition to the potential quality of life benefit, the most important question of whether the use of a cytoprotective agent might translate into the possibility of maintaining the dose intensity of anticancer therapies has still to be answered. The real benefit of amifostine in the overall management of patients with cancer requires additional studies to determine whether this chemoprotective approach can be of benefit to patients by increasing response rate, time to progression, and long term survival in patients receiving the more recent combination therapies involving new drugs such as the taxanes and oxaliplatin.
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PMID:A risk-benefit assessment of amifostine in cytoprotection. 1055 52

This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2)at day 1-3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m(2/)d over 18 h), ifosfamide (4 g/m(2)/d over 4 h) and etoposide (500 mg/m(2)/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 microg kg(-1)subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min(-1)) and 37% in the control patient group (107 to 67 ml min(-1)) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumin and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT3-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 microl(-1))and thrombocytes (> 25 000 microl(-1))were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the amifostine arm. The reduction of acute toxicity observed in the amifostine arm resulted in 30% savings in costs for supportive care (Euro 4396 versus Euro 3153 per patient). Taking into account the drug costs of amifostine, calculation of in-patient treatment costs from the start of chemotherapy to discharge revealed additional costs of Euro 540 per patient in the amifostine arm. This randomized pilot study indicates that both organ and haematotoxicity of HD-VIC chemotherapy can be ameliorated by the use of amifostine. Additionally, a nearly complete preservation of GFR was observed in amifostine-treated patients which may be advantageous if repetitive cycles of HDCT are planned. Larger randomized trials evaluating amifostine cytoprotection during high-dose chemotherapy are warranted.
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PMID:A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation. 1116 94

This phase II trial was designed to verify that subcutaneous (SC) administration of Amifostine (Ethyol) protects against radiation therapy (RT)-induced xerostomia and ameliorates amifostine-related side effects (including nausea, vomiting, and hypotension). Patients receiving amifostine SC plus RT had a 56% incidence of acute xerostomia, comparable with previous phase III data with intravenous administration of amifostine. There was good tolerability, with cutaneous toxicity as the most significant side effect. These data suggest that amifostine SC provided comparable protection against RT-induced acute xerostomia as amifostine intravenously.
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PMID:A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer. 1191 79

Dermatomyositis is associated with malignancy in approximately 20-25% of cases. The most common associated cancers are ovarian, lung, pancreatic, stomach, colon and non-Hodgkin's lymphoma. Nasopharyngeal cancer is not common in the Caucasian population; however, there is a much higher incidence in Asian patients. Radiotherapy is the mainstay of treatment for early nasopharyngeal cancer, but combination chemoradiotherapy is becoming more common for patients with advanced disease since the Intergroup trial 0099 demonstrated improved progression-free survival and overall survival for chemoradiotherapy. Increasingly, the cytotoxic agent amifostine is being used prior to radiotherapy in an attempt to decrease associated morbidities. Amifostine has been found to significantly decrease acute and chronic xerostomia but not mucositis. It appears to be selectively protective to salivary glands and kidneys without being tumor protective. The most common side effects associated with amifostine are nausea, vomiting, hypotension, hypocalcemia and allergic reactions. We describe the case of a man with dermatomyositis and stage IV nasopharyngeal cancer treated with chemoradiotherapy and s.c. amifostine. The patient suffered a life-threatening anaphylactoid reaction to amifostine.
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PMID:Life-threatening anaphylactoid reaction to amifostine used with concurrent chemoradiotherapy for nasopharyngeal cancer in a patient with dermatomyositis: a case report with literature review. 1198 77

Due to concerns about toxicity, many elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are not considered candidates for standard chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). The cytoprotective agent amifostine has the potential to reduce toxicity when added to chemotherapy. The purpose of the current study was to examine the toxicity of CHOP combined with amifostine in elderly patients with aggressive NHL. A prospective phase II study was performed in patients aged 60 years and older. Patients with stage I/II disease received 4 cycles of CHOP followed by involved-field irradiation. Patients with stage III/IV received 6-8 cycles of CHOP. Amifostine (740 mg/m(2)) was administered as a 15-min i.v. infusion immediately before chemotherapy. Forty-one (median age 69.5 years, range 60-87) of 49 consecutive previously untreated patients, aged 60 years and older, with aggressive NHL seen in our center were included in the study. Twenty-one patients had stage I/II disease and 20 had stage III/IV disease. The patients received a total of 207 cycles of amifostine-CHOP. Infusion of amifostine caused mild to moderate transient side effects, including a drop of systolic blood pressure >20 mmHg in 54 cycles and nausea/vomiting in 36 cycles. Hematotoxicity of CHOP consisted of leukopenia grade 4 in only 15.4% of cycles. There were two cases of grade 3 anemia. No thrombocytopenia higher than grade 2 occurred. Febrile neutropenia was rare, occurring in 4.3% of cycles. One patient died after the first CHOP administration because of anthracycline-related acute cardiomyopathy (corresponding to a toxic death rate of 2.4%). The complete response rates were 85 and 75% in stage I/II and stage III/IV patients, respectively. After median follow-up of 33 months (range 17-50 months) the median overall survival was not reached in patients with stage I/II and was found to be 32 months in patients with stage III/IV. At 2 years, 76% of patients with stage I/II and 70% with stage III/IV were alive. Twelve of the 15 patients who died were aged older than 70. Amifostine pre-treatment was associated with a low toxicity of CHOP in elderly patients with aggressive NHL treated with curative intent. Treatment outcomes appeared not to be impaired by the addition of amifostine to CHOP. This schedule merits further testing in a randomized trial.
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PMID:Influence of amifostine on toxicity of CHOP in elderly patients with aggressive non-Hodgkin's lymphoma--a phase II study. 1198 85

Amifostine treatment may allow chemotherapy dose increases beyond those permitted by autologous hematopoietic stem cell transplantation. In a recent study in patients with solid tumors receiving a high-dose regimen of etoposide, ifosfamide, and carboplatin plus autologous stem cell transplantation, amifostine pretreatment was associated with significant reductions in time to neutrophil and thrombocyte engraftment, fewer days of neutropenic fever, less need for salvage antibiotic therapy. Also, there were significant reductions in grade 3 or 4 stomatitis/diarrhea, and delayed nausea/vomiting. A phase I/II study in patients with refractory/high-risk malignancies indicated that a 140% increase of high-dose melphalan (up to 280 mg/m2) can be safely used with amifostine and autologous stem cell transplantation with manageable mucosal toxicity and a reduced incidence of regimen-related toxicity. Preliminary findings in another phase II study indicate that melphalan 280 mg/m2 can also be safely used with amifostine/stem cell transplantation in the treatment of patients with myeloma. Additional studies are ongoing or planned to examine the potential hematoprotective and hematostimulating effects of amifostine in the setting of high-dose chemotherapy and autologous stem cell transplantation.
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PMID:The potential of amifostine in high-dose chemotherapy and autologous hematopoietic stem cell transplantation. 1257 45

The availability of subcutaneously (SC) administered amifostine may present an advantage for radioprotectant therapy in head and neck cancer patients. In a randomized phase II trial comparing SC amifostine versus no amifostine in 140 patients undergoing radiation therapy for head and neck, thoracic, or pelvic cancers, amifostine treatment was associated with reductions in mucosal toxicity and delays in radiation therapy among the 19 patients with head and neck cancer, as well as in the thoracic and pelvic cancer groups. A phase II trial of SC amifostine in head and neck cancer was performed in a patient population (n = 54) similar to that studied in a phase III trial of intravenous amifostine to allow comparisons of outcomes. Acute xerostomia grade 2 occurred in 56% with SC amifostine and 51% with intravenous amifostine (78% in the no-amifostine group in phase III trial), with median time to onset being 40 days and 45 days, respectively (30 days with no amifostine), and cumulative radiation dose to onset being 58 Gy and 60 Gy (42 Gy with no amifostine), respectively. Amifostine SC was well tolerated, with three quarters of patients receiving > or =75% of the planned dose. Nausea, vomiting, and hypotension were less severe with SC amifostine, but cutaneous toxicity was more frequent. The reduction in radiation therapy-induced acute xerostomia with SC amifostine is similar to that with intravenous amifostine in patients with head and neck cancer. If cutaneous toxicity is judged an acceptable risk, SC amifostine may represent a second, more convenient option for treating physicians.
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PMID:Phase II trial of subcutaneous amifostine in patients undergoing radiation therapy for head and neck cancer. 1257 50

This ongoing study was initiated to determine the feasibility of administering amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) with monomodal high-dose rate (mHDR) brachytherapy and to assess the tolerability and side effects of this combination. To date, 18 patients suitable for prostate implant brachytherapy (<or=T2aN0; prostate-specific antigen <or= 10 ng/mL; Gleason score <or= 6) have been treated with mHDR brachytherapy, receiving four 9-Gy fractions administered twice daily for 2 days. Amifostine (500 mg) is administered subcutaneously on the day before implant and 30 to 60 minutes before the first and third mHDR treatments. All 18 patients have received amifostine and brachytherapy as planned. Nausea was manageable with oral prochlorperazine in the pretreatment phase and our standard antiemesis protocol (intravenous promethazine, with granisetron if needed) during the implant; hypotension and asthenia were not problematic. During the 2-week post-treatment phase, grade 1 cystitis occurred in eight of 18 patients; grades 1 and 2 proctitis occurred in six of 18 and five of 18 patients, respectively. Six patients developed urinary obstruction symptoms. Preliminary results support the feasibility and tolerability of subcutaneous amifostine in conjunction with mHDR brachytherapy. Total accrual goal is 50 patients to assess long-term efficacy. Additional studies of HDR with amifostine are planned for patients with recurrent prostate and gynecologic cancer.
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PMID:Feasibility of amifostine administration in conjunction with high-dose rate brachytherapy. 1472 40


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