Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The new anthracyclin, menogaril [7-(R)-0-methylnogarol], is reported to produce less cardiotoxicity than doxorubicin after multiple doses. This study was designed to assess acute hemodynamic changes during the first administration of menogaril and to relate these changes to plasma concentrations. Menogaril (200 mg/mg) was infused over 90 minutes to 4 patients with metastatic colon or prostate cancer. Cardiac output (CO) and stroke volume (SV) were measured noninvasively by Doppler ultrasound. Menogaril plasma concentrations were measured by HPLC and a 3-compartment mammillary model was used for pharmacokinetic analysis of the results. Steady-state volume of distribution, elimination clearance, and elimination half-life averaged 1,114 +/- 340 l/m2, 38 +/- 16 l/h/m2 and 40.3 +/- 30.3 hours, respectively. All patients were normotensive (baseline blood pressure = 135 +/- 10/73.5 +/- 8 mmHg) and ejection fractions were in normal range (EF = 68 +/- 7%). Transient increase in mean arterial pressure (MAP) from 93 +/- 3 to 107 +/- 4 mmHg (p < or = 0.001) were seen during and shortly after the end of menogaril infusion in all patients. Heart rate (78 +/- 5 min-1) remained constant. CO fell slightly and total peripheral resistance (TPR) increased by 36.8% in the last 2 patients. The increase in MAP was analyzed by a linear-effect model and averaged 0.028 +/- 0.017 mmHg per ng/ml of menogaril in the hypothetical biophase. The half-life for menogaril equilibration between plasma and this biophase was 41 +/- 22 minutes. We conclude that during acute administration of menogaril, blood pressure increases transiently secondary to an increase in TPR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics and acute cardiovascular effects of menogaril in patients with metastatic tumors. 775 12

Menogaril is a semisynthetic anthracycline that is less cardiotoxic than doxorubicin in a preclinical model. We conducted a phase II trial to determine the activity of menogaril in hormone-refractory prostate cancer. Between October 1985 and November 1987, 32 eligible patients were enrolled and were divided into good- and poor-risk categories, the latter being defined by prior radiotherapy to less than one third of the marrow-containing skeleton. Good-risk patients received a starting dose of 200 mg/m2 by 60-minute IV infusion, whereas the poor-risk patients received 160 mg/m2. Treatment was repeated every 3 weeks until disease progression. Menogaril caused leukopenia in 90% of patients, of whom 47% had grade III or IV toxicity. Thrombocytopenia was uncommon and mild, with only three patients (9%) experiencing grade II toxicity. Nonhematologic toxicity included mucositis (9%), and mild weight loss in 33% of patients. Nine patients (28%) had stable disease of 3 or more months' duration. There were no objective partial or complete responses. The median time to progression for the entire group was 10 weeks, and the median survival time for all patients was 24 weeks. Because of appreciable toxicity and limited antitumor activity, further study of menogaril cannot be recommended in hormone-refractory prostate cancer.
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PMID:Phase II evaluation of menogaril in advanced prostate cancer: Eastern Cooperative Oncology Group EST P-A885. 1131 90