menogaril and Ovarian-Neoplasms

Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma; Cisplatin; Drug Evaluation; Female; Humans; Menogaril; Middle Aged; Nogalamycin; Ovarian Neoplasms; Recurrence; Remission Induction; Survival Analysis

Eight human ovarian cancer lines grown in nude mice were used to compare the activity of doxorubicin, epirubicin, mitoxantrone and menogaril. The tumour lines were different in histological subtype, tumour doubling time and sensitivity to doxorubicin. The compounds were administered intravenously at the maximum tolerated dose twice with one week in between when tumours measured 50-150 mm3. Growth inhibition greater than 50% was obtained for doxorubicin in 8/8, for epirubicin in 4/8, for mitoxantrone in 5/8 and for menogaril in 2/8 tumour lines. In MRI-H-207, doxorubicin was the only drug able to induce complete remission. Compared with doxorubicin, mitoxantrone and menogaril were given in proportionally higher doses than those administered to patients, but did not result in superior antitumour activity.

Topics: Animals; Antineoplastic Agents; Cell Line; Dose-Response Relationship, Drug; Doxorubicin; Epirubicin; Female; Menogaril; Mice; Mice, Nude; Mitoxantrone; Nogalamycin; Ovarian Neoplasms

Topics: Adult; Aged; Antineoplastic Agents; Daunorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Intravenous; Menogaril; Middle Aged; Nogalamycin; Ovarian Neoplasms

The activity of menogaril and its major metabolite in animals and humans, N-demethylmenogaril, has been investigated in the human stem cell assay as developed by Salmon et al. Among 31 evaluable samples, four were sensitive to menogaril, including one which responded to N-demethylmenogaril. Three samples resistant to menogaril responded to N-demethylmenogaril. None was sensitive to doxorubicin. Overall, one out of seven ovarian samples and one out of three breast samples responded to menogaril. Our data confirm the in vitro activity of menogaril in ovarian and breast cancer; in addition, they suggest incomplete cross-resistance between doxorubicin and menogaril and, considering the concentrations of N-demethylmenogaril in animals and humans, a minor role for this metabolite in the overall antitumor activity of the parent compound.

Topics: Breast Neoplasms; Cell Survival; Daunorubicin; Dose-Response Relationship, Drug; Female; Humans; Menogaril; Neoplastic Stem Cells; Nogalamycin; Ovarian Neoplasms; Tumor Stem Cell Assay