Mitomycin-C in breast cancer

Mitomycin-C, an antitumor antibiotic discovered in 1958, acts as a bifunctional alkylating agent. Initial clinical trials utilized a daily schedule of administration, which led to severe and protracted myelosuppression and inadequate evaluation of the antitumor spectrum of mitomycin-C. In the early 1970s, the intermittent high-dosage schedule of administration was developed: 20 mg/m2 of mitomycin-C intravenously, every 6 to 8 weeks. An overall response rate of 35% was reported by several investigators. Subsequently, other administration schedules were attempted without improvement in therapeutic index. More recently, mitomycin-C was used in combinations with other drugs. Combinations of mitomycin-C and one of the vinca alkaloids have produced response rates of approximately 30% to 40% in patients with extensive previous treatment. In patients not previously exposed to doxorubicin, combinations of mitomycin-C and doxorubicin have offered response rates of approximately 50%. Acute toxicities of mitomycin-C are tolerable and consist of mild nausea, vomiting, and anorexia. Chronic toxicities include cumulative myelosuppression--especially thrombocytopenia--pulmonary toxicity, renal toxicity, and occasionally cardiac toxicity. Mitomycin-C is an effective antitumor agent in breast cancer and should be carefully incorporated in the therapeutic strategy of this disease.