A phase I-II study of continuous 5-day infusion mitomycin-C

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Advanced metastatic breast and gastrointestinal malignancies often develop drug resistance.
• Mitomycin-C is an established chemotherapeutic agent, but its optimal administration for resistant cancers requires investigation.

Purpose of the Study:

• To determine the maximum-tolerated dose (MTD) of continuous 5-day infusion mitomycin-C.
• To evaluate the efficacy of this regimen in patients with advanced metastatic, drug-resistant breast and gastrointestinal cancers.

Main Methods:

• Phase I-II clinical trial design.
• Continuous 5-day infusion of mitomycin-C.
• Dose escalation to identify MTD and dose-limiting toxicities.
• Assessment of patient response and toxicity in breast and gastrointestinal cancer cohorts.

Main Results:

• The dose-limiting toxicity was severe and cumulative myelosuppression, primarily thrombocytopenia.
• Well-tolerated doses were 3 mg/m²/day for 5 days (repeated every 6-8 weeks) for breast cancer patients.
• MTD was 4 mg/m²/day for gastrointestinal cancer patients.
• One partial response in breast cancer (lasting 4 months); no responses in gastrointestinal cancer.
• Nonhematologic, renal, and cardiac toxicities were infrequent.

Conclusions:

• Continuous infusion mitomycin-C demonstrated significant myelosuppression as the primary dose-limiting toxicity.
• The therapeutic index of mitomycin-C did not appear to be improved by continuous infusion in this patient population.
• Limited efficacy observed in heavily pre-treated patients with drug-resistant advanced cancers.