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Evaluation of menogaril in patients with metastatic sarcomas and no prior chemotherapy exposure
J C Buckner1, J H Edmonson, J N Ingle
1Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905.
Abstract:
Menogaril, an anthracycline analog of nogalamycin, is reported to have greater cytotoxicity against certain malignant cell lines and less cardiotoxicity in rabbits than doxorubicin. To evaluate the possible therapeutic benefit of this drug, we studied menogaril in 21 patients with metastatic sarcomas who had received no prior chemotherapy. Menogaril was administered intravenously over 1 h every 3-4 weeks at a dose of 200 mg/m2 in 500 ml of 5% dextrose in water. One patient experienced a partial regression of pulmonary metastases from malignant fibrous histiocytoma of bone (response rate of 5% with 95% confidence interval of 0.1-23.8%). Two additional patients experienced minor reductions in tumor size. The remaining 18 patients had no improvement from menogaril. The median time to disease progression was 7 weeks in all patients treated. Toxicity was acceptable, consisting primarily of leukopenia with 12 patients (57%) and 19 patients (90%) developing nadir leukocyte counts less than 2000 and 3000/microL, respectively. Cardiac toxicity was not encountered; however, only seven patients received greater than or equal to 3 cycles of menogaril. We conclude that menogaril does not appear to be useful at this dose and schedule in the treatment of metastatic sarcomas despite the use of near maximal doses in patients with no prior chemotherapy exposure.
Insights
Menogaril showed limited efficacy in treating metastatic sarcomas, with only one partial response observed. Further research is needed to determine its therapeutic potential in cancer treatment.
Area of Science:
- Oncology
- Pharmacology
Background:
- Menogaril, an anthracycline analog, demonstrated promising preclinical results with higher cytotoxicity and lower cardiotoxicity than doxorubicin.
- Metastatic sarcomas represent a challenging group of cancers with limited treatment options.
Purpose of the Study:
- To evaluate the therapeutic benefit of menogaril in patients with metastatic sarcomas.
- To assess the efficacy and toxicity profile of menogaril in a chemotherapy-naive patient cohort.
Main Methods:
- A phase II clinical trial was conducted involving 21 patients with metastatic sarcomas.
- Menogaril was administered intravenously at a dose of 200 mg/m2 every 3-4 weeks.
- Tumor response, disease progression, and toxicity were monitored.
Main Results:
- A 5% objective response rate was observed, with one patient achieving partial regression of pulmonary metastases.
- The median time to disease progression was 7 weeks.
- Leukopenia was the primary toxicity, but cardiac toxicity was not observed in this cohort.
Conclusions:
- Menogaril demonstrated limited clinical activity in metastatic sarcomas at the studied dose and schedule.
- The drug's efficacy does not appear sufficient for this patient population, despite acceptable toxicity.
- Further investigation into alternative dosing or combination strategies may be warranted.
