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Phase I study of oral menogaril administered daily for 14 consecutive days
D J Stewart1, S E Aitken, S Verma
1Ontario Cancer Treatment & Research Foundation Ottawa Regional Cancer Centre, Canada.
Abstract:
Twenty-eight patients were treated with oral menogaril daily x 14 every 4 weeks. Granulocytopenia was dose-limiting at 50-60 mg/m2 per day. Neutropenic fever occurred in one patient. Thrombocytopenia occurred in 3 of 6 patients treated with menogaril 60 mg/m2/day. Nausea and vomiting and other toxic effects were generally mild. No cardiac toxicity was seen. One partial remission and three minor responses were noted among 11 previously treated patients with carcinoma of the bladder. One minor response was noted among 3 patients with colorectal cancer. The dose recommended for phase II studies is 50 mg/m2 per day for 14 days. Phase II studies are recommended in carcinoma of the bladder. Gastrointestinal toxicity is substantially less on this schedule than with oral menogaril administered on a weekly or q4wk schedule, but thrombocytopenia may be more common.
Insights
Oral menogaril at 50 mg/m2 daily for 14 days showed efficacy in bladder cancer. This dosing schedule resulted in manageable toxicity, with gastrointestinal side effects reduced but a potential increase in thrombocytopenia.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Menogaril is an anthracycline antibiotic investigated for cancer treatment.
- Previous administration schedules of oral menogaril have been associated with varying toxicity profiles.
- Understanding optimal dosing and scheduling is crucial for maximizing therapeutic benefit and minimizing adverse events.
Purpose of the Study:
- To evaluate the safety and efficacy of oral menogaril administered daily for 14 days every 4 weeks.
- To determine the dose-limiting toxicities and recommend a dose for Phase II studies.
- To explore the activity of this menogaril schedule in patients with advanced solid tumors, particularly bladder and colorectal cancer.
Main Methods:
- Twenty-eight patients with advanced solid tumors received oral menogaril.
- Treatment involved daily administration for 14 days, with cycles repeated every 4 weeks.
- Dose escalation was employed to identify dose-limiting toxicities, with granulocytopenia noted at 50-60 mg/m2/day.
- Tumor response was assessed in patients with bladder and colorectal cancer.
Main Results:
- Granulocytopenia was identified as the dose-limiting toxicity at 50-60 mg/m2/day.
- Thrombocytopenia occurred in 3 of 6 patients at the 60 mg/m2/day dose.
- Mild nausea and vomiting were common, but overall gastrointestinal toxicity was less severe than with other schedules.
- One partial remission and three minor responses were observed in 11 patients with bladder cancer.
- One minor response was noted in 3 patients with colorectal cancer.
Conclusions:
- The recommended dose for Phase II studies of oral menogaril is 50 mg/m2/day for 14 days.
- Phase II studies are warranted, particularly in patients with carcinoma of the bladder.
- This schedule demonstrates reduced gastrointestinal toxicity compared to weekly or q4wk schedules, though thrombocytopenia may be more frequent.