Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New triplet chemotherapy combinations are under investigation in advanced non small cell lung cancer (NSCLC). Carboplatin, plus paclitaxel, plus gemcitabine is among the most active and promising regimens. The use of more aggressive chemotherapy in order to improve results can increase toxicity. Amifostine (WR-2721) reduces toxicity of radiotherapy and chemotherapy and protects selectively a number of normal, but not neoplastic, tissue. Based on this background, we performed a phase II study on carboplatin, plus paclitaxel, plus gemcitabine with amifostine support in advanced NSCLC. Patients received chemotherapy at the following dosage: carboplatin AUC 5, i.v., at day 1; paclitaxel 175 mg/m2, i.v. by 3-hour infusion, at day 1; gemcitabine 1000 mg/m2, i.v. by 3-hour infusion, at days 1 and 8; every 3 weeks for a maximum of 6 cycles. Amifostine was administered at the dose of 740 mg/m2, i.v., at day 1 of each cycle. Seventeen patients entered the study. They were prevalently male, median age was 62 years, PS (ECOG) was 0 in 10 cases (58.8%), 1 in 6 (35.3%) and 2 in 1 (5.9%). Histology was epidermoid in 8 cases (47%) and adenocarcinoma in 9 (53%). We observed 8 (47.5%) objective responses with 2 (11.7%) complete responses. Median time to progression and median survival were 24 and 36 weeks, respectively. Treatment was well tolerated. The main toxicity was as follows: grade 3 neutropenia, grade 2 thrombocytopenia and grade 3 anemia in one (5.8%) case; grade 2 peripheral neurologic toxicity in 3 (17.6%) patients; grade 2 cardiac toxicity (atrial fibrillation) in one case; and grade 3 respiratory toxicity (dispnoea) in one patient. These data indicate that this combination has promising activity and tolerability. A randomized trial comparing carboplatin plus paclitaxel, plus gemcitabine versus carboplatin, plus paclitaxel, plus gemcitabine, plus amifostine in advanced NSCLC is warranted.
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PMID:New triplet chemotherapy combination with carboplatin, paclitaxel and gemcitabine plus amifostine support in advanced non small cell lung cancer: a phase II study. 1126 91

The authors discuss the results of 3 studies of their group reflecting the possible role of amifostine in simultaneous radiochemotherapy (RCT) of advanced head and neck cancer. In a controlled phase II trial (1995 through 1996), 39 patients were included in this pilot investigation. A control group (n = 14) received simultaneous RCT of the head and neck region with an irradiation dose of 60 Gy and 2 cycles of carboplatin (700 mg/m(2) cumulative dose). Twenty-five patients received the same basic therapy and an additional 500-mg dose of amifostine before each chemotherapy. Amifostine was administered less than 45 minutes before the end of radiotherapy. The authors observed a dramatic reduction of typical radiotherapy-associated toxicities (mucositis, xerostomia, loss of taste, dysphagia). The hematologic side effects (leukocytopenia, anemia, thrombocytopenia) also were decreased significantly. The overall survival rate and locoregional control of both groups were comparable after 12 months. In a controlled intensification trial (1997 through 1999), the authors included 76 consecutive patients (69 men, 7 women) with pharyngeal cancer (oropharynx, n = 33; hypopharynx, n = 43). The tumors were characterized as unresectable and locally advanced without distant metastasis. All patients received a conventional radiotherapy (2-Gy single dose, daily fractionation) up to doses of 60 Gy and an additional 10 Gy as a boost in the tumor-infiltrated region. A dose of carboplatin, 70 mg/m(2), was given to a group of 45 patients on days 1 through 5 and 29 through 33 of radiotherapy (RCT arm). The resulting cumulative dose was 700 mg/m(2). A group of 31 patients (RCTintens arm) received the same dose of carboplatin on days 1 through 5, 22 through 26, and 43 through 47 or 1 through 5, 15 through 19, 29 through 33, and 43 through 47 of radiotherapy (cumulative dose 1.05 to 1.40 mg/m(2)). All patients received 500 mg of amifostine before each carboplatin administration. If the tumor volume was less than 20 cm(3), we observed an increased 1-year overall survival rate (91% v 71%) and time to progression (17 months v 10 months). If the tumor volume was greater than 20 cm(3), we observed comparable treatment results in both groups (1-year survival rate, 60% v 61%; time to progression, 13 months v 12 months). In a long-term follow-up investigation (1999 through 2000), 531 patients (89 women, 442 men) were analyzed according to their toxicities during regular follow-up investigations at our outpatient facility. All patients were treated by surgery or radio(chemo)therapy because of an advanced head and neck cancer. A total of 218 of 531 patients received the antineoplastic therapy without cytoprotection. An additional 313 patients received their RCT combined with amifostine administration before administration of the radiosensitizer. A significant influence of cytoprotection was registered in the following toxicities: xerostomia, fibrosis, loss of taste, and dysphagia. No impact was seen on the development of interstitial lymph edema and esophageal stenosis. Amifostine could be integrated in simultaneous radiochemotherapy of advanced head and neck cancer patients. The authors favor the administration of amifostine before chemotherapeutics alone. Selective cytoprotection could decrease the main acute toxicities (mucositis, xerostomia, dysphagia) as well as late side effects (xerostomia, loss of taste, fibrosis) of this form of combined treatment. The enhanced therapeutic index may be changed into a prognostic benefit for selected patients with unresectable tumors, if the volume is smaller than 20 cm(3).
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PMID:Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer. 1191 77

Amifostine (AMF) promotes in vitro growth and survival of hematopoietic progenitors. In this study we evaluated the efficacy of AMF in the treatment of anemia in patients with low-risk myelodysplastic syndromes (MDS) and the possible predicting value for response to AMF therapy of two types of in vitro clonogenic assays. Two different doses of AMF, 300 mg/m2 (group A, 11 patients) or 400 mg/m2 (group B, 16 patients), were studied. AMF was given three times weekly for 3 weeks, i.v., followed by 2 weeks off therapy. Patients were evaluated after two cycles of treatment. Partially or nonresponding patients of group A received 400 mg/m2 AMF and were reevaluated. An increase of hemoglobin (Hb) values of more than 2 g/dl and a 100% decrease in transfusion requirements for at least 6 weeks were defined as a complete response (CR) while an increase of Hb values of 1-2 g/dl or a 50% decrease in transfusion requirements was considered as a partial response (PR). In group A, two out of 11 (18.1%) patients achieved a CR with the initial dose and one of the nine that received 400 mg/m2 AMF achieved a PR. In group B, three out of 16 (18.7%) patients achieved a PR; the overall response rate in both groups was 22.2%. In group A, bone marrow progenitor assay was performed pre- and post-amifostine treatment. Erythroid burst-forming units (BFU-E) were increased in six out of 11 (54.5%) patients, and this increase preceded the rise in Hb levels in three of them. In group B, a clonogenic assay was performed in 11 out of 16 patients before AMF treatment. In vitro results after pretreatment with 500 microM amifostine confirmed the response of two MDS patients that achieved a PR. No response in vitro was observed in all eight nonresponding patients and in one PR patient. The lack of response in the clonogenic assays predicted for nonresponse to treatment with a predictive power of 91.8%. We conclude that 300 mg/m2 is an adequate initial treatment for low-risk MDS patients and both clonogenic assays have a strong predicting value for response to treatment.
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PMID:Treatment of anemia in low-risk myelodysplastic syndromes with amifostine. In vitro testing of response. 1197 18

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

Myelodysplastic syndrome (MDS) is a clonal disease of the bone marrow characterized by abnormal hematopoiesis and cytopenias. It has been shown that abnormal cytokine production together with apoptosis are major contributors to the cytopenias associated with the disorder. As the interaction of cytokines plays a role in the pathogenesis, suppression of the cytokine production by the administration of the combination of pentoxifylline, ciprofloxacin, and dexamethasone (PCD combination) has resulted in the correction of at least some aspects of the cytopenias in the majority of patients and in complete hematologic remission in a small percentage. The aminothiol prodrug amifostine, a compound to protect tissues from cytotoxic drugs and radiotherapy has been found to stimulate proliferation of normal hematopoiesis and suppress apoptosis in patients with MDS. In this study we report the results of combination therapy of amifostine and PCD in 12 patients with MDS and acute myeloid leukemia (AML). Amifostine was given in a dose of 200 mg/m(2), as an i.v. infusion administered in 10 min, three times a week; pentoxifylline 2400 mg/day, (3 x 800 mg) p.o.; ciprofloxacin, 1 g/day p.o.; dexamethasone 4.5 mg/day p.o. We achieved 66% response rate in our patients. In some cases responses were achieved in only thrombocytopenia or anemia whereas in others responses were achieved in multiple series. As a result it was found that amifostine + PCD combination may be beneficial in reversing cytopenias in the treatment of MDS and AML and is worth further study.
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PMID:Results of combination therapy with amifostine, pentoxifylline, ciprofloxacin and dexamethasone in patients with myelodysplastic syndrome and acute myeloid leukemia. 1885 92