menogaril and Neoplasm-Metastasis

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)

Topics: Aged; Arrhythmias, Cardiac; Blood Pressure; Cardiac Output; Colonic Neoplasms; Female; Half-Life; Hemodynamics; Humans; Male; Menogaril; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Vascular Resistance

Menogaril, a new semisynthetic anthracycline antibiotic, was administered to 35 patients with advanced colorectal cancer. The drug was infused over 2 hr at a dose of 160 mg/sqm or 200 mg/sqm repeated every 4 weeks. Twenty-seven patients were evaluable for response and no objective responses were achieved. Myelosuppression, only leukopenia, was usually of mild-moderate degree and occurred in 63% of the patients. Twenty-seven percent of the patients experienced severe leukopenia. Local erythema and phlebitis were frequently observed and were severe in 13% of the patients. Nausea/vomiting (66%) and alopecia (50%) were. of mild-moderate degree. This study suggests that menogaril at these doses and schedule had no activity in advanced colorectal cancer.

Topics: Adult; Aged; Antineoplastic Agents; Colorectal Neoplasms; Daunorubicin; Drug Administration Schedule; Drug Evaluation; Female; Hematologic Tests; Humans; Male; Menogaril; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Nogalamycin

A total of 25 patients with metastatic breast cancer who had failed one prior chemotherapy regimen and had not received prior treatment with doxorubicin were treated with menogaril (200 mg/m2 i.v. over 1 h) every 4 weeks. Four patients (16%) achieved partial regressions lasting a median of 46 days. The median time to progression for all patients was 60 days and the median survival was 264 days. Seventeen patients subsequently received doxorubicin after removal from protocol and six (35%) achieved objective regression. We conclude that menogaril administered by the method that we employed has marginal activity in women with metastatic breast cancer after failure of prior chemotherapy. Failure to respond to menogaril does not preclude response to subsequent treatment with doxorubicin.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Daunorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Menogaril; Neoplasm Metastasis; Nogalamycin