Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Etoposide was found to be schedule-dependent in both preclinical and clinical trials. A study was initiated in March 1988 at Indiana University (Indianapolis, IN), using daily oral etoposide in patients with refractory germ cell tumors. The dose was 50 mg/m2/d, administered daily until progression or toxicity not ameliorated by dose adjustment occurred. Twenty-two patients have been entered to date. Primary sites were testis (11 patients), retroperitoneum (five patients), and mediastinum (six patients). All 22 patients had had previous treatment with cisplatin/etoposide combination regimens, including six patients who were also previously treated with high-dose etoposide and carboplatin with autologous bone marrow transplantation. The median number of treatment regimens was 2.9 (range, 1 to 4). Five patients had progressive disease during treatment with etoposide. Median length of treatment was 11.5 weeks (range, 2 to 30), with six patients continuing on treatment. Median white blood cell nadir was 1.5 x 10(9)/L, median hemoglobin nadir 9.1 g/dL, and the median platelet nadir 184,000/microL. Granulocytopenia required temporary cessation of treatment in eight patients and dose reductions in four. Five patients developed granulocytopenic fevers, including pneumonia (two patients) and bacteremia (one patient). Additionally, two patients (who tested negative for human immunodeficiency virus) died from Pneumocystis pneumonia with granulocyte counts higher than 500/microL. Of 21 evaluable patients (there was one protocol violation), three responded with a greater than 90% decrease in markers and a greater than 50% decrease in measurable radiographic disease. One of these had previously progressed on cisplatin/etoposide combination therapy. Three other patients responded with a greater than 90% decrease in markers but with stable radiographic disease; two of them had previously resected teratoma. The remaining ten patients were nonresponders. In conclusion, daily oral etoposide has definite activity in refractory germ cell tumors. Further evaluation of this regimen is warranted.
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PMID:Phase II study of daily oral etoposide in refractory germ cell tumors. 215 58

The purpose of this study was to examine the antitumor activity, toxic effects, and plasma pharmacokinetics of fractionated doses of oral etoposide aiming at the achievement of prolonged safe and active plasma drug levels in patients with AIDS-related Kaposi sarcoma (KS). This was designed as a phase II trial in which consecutive patients with progressing AIDS-KS after at least 3 months of active antiretroviral therapy received oral etoposide at the dose of 20 mg/m2 every 8 hours daily for 7 days every 21 days, with the study of its plasma pharmacokinetics. Eligible patients were 18 to 60 years old, with a histopathologically confirmed diagnosis of AIDS-related KS, human immunodeficiency virus-positive test, progressing after at least 3 months of active antiretroviral therapy, World Health Organization (WHO) performance status 0 to 3, New York University staging IIA or greater, no active infection except oral candidiasis, normal bone marrow, liver, and renal function, and who signed an informed consent. Objective tumor responses were evaluated after at least one full treatment course according to a modified WHO criteria, and toxicity was evaluated weekly and graded using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) criteria. For the pharmacokinetic study, plasma was obtained from patients during the first drug administration immediately before and at various time points thereafter. Etoposide was measured after extraction from plasma by a standard high-performance liquid chromatography. Twenty-one patients were accrued for the study, and 18 of them met the eligibility criteria. They were all men, with median age of 36 years old (range: 25-50 years), median WHO performance status 0 (range: 0-3) median CD4+ count (cells/mm3) 67 (range: 8-443), prior AIDS diagnosis in 10 of 18 cases, NYU staging IIA (1 patient), IIB (1), IIIA (7), IIIB (1), IVA (4), and IVB (4) sites of disease: mucocutaneous only (5), mucocutaneous/lymph nodes (5), mucocutaneous/lung (5) and mucocutaneous/lymph nodes/lung (2); and prior cytotoxic treatment in two patients. Seventy-two percent of cases presented some form of toxic effect (NCI-CTC). Leukopenia was documented in 50% of cases, anemia occurred in 61%, whereas thrombocytopenia was documented in 17% of the patients. The main nonhematologic toxicities were nausea and vomiting in 17% of cases and alopecia in 44%. The overall objective response rate was 83%, with 2 complete remissions documented (11%). The median duration of responses was 12 weeks (range: 3-45 weeks). The median t1/2 of etoposide in plasma was 4.11 hours (range: 1.95-9.64), area under the curve was 13.51 microg/h/ml (range: 7.12-24.42), Cmax was 2.17 microg/ml (1.40-4.41), tmax (1.00-2.00), mean residence time 4.62 hours (range: 3.75-5.20 hours), CIt (total clearance) 3.13 l/m2/h (range: 1.49-5.20 l/m2/h), Vd 13.08 l/m2 (range: 6.23-19.65 l/m2), and the median etoposide plasma concentration time greater than 1 microg/ml was 3.69 hours (range: 1.00-6.80 hours). The use of fractionated oral daily doses of etoposide produced significant antitumor activity with manageable clinical toxicity in the individuals with AIDS-KS included in this trial. This more favorable therapeutic index of etoposide could be due to the achievement of more sustained plasma levels of the drug within safe but active concentrations.
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PMID:Fractionated doses of oral etoposide in the treatment of patients with aids-related kaposi sarcoma: a clinical and pharmacologic study to improve therapeutic index. 1131 95