ABSTRACT
In 1956, Hata et al.1 at the Kitasato Institute isolated mitomycins A and B by chromatography of a mixture compounds from cultures of Streptomyces caespitosis. A subsequent investigation on the same organism by Wakaki’s group at Kyowa Fermentation Industry yielded mitomycin C, which proved to be the most active anticancer agent among these, and subsequent, natural mitomycins.2 Mitomycin C (Chart 23.1) was introduced as an anticancer drug by Kyowa, and it caught on rapidly.3 It was given to an estimated 60% of patients receiving chemotherapy in Japan during the 1960s. In contrast, the œrst clinical trials in the United States were very unsatisfactory, with 11 patients dying from the effects of myelosuppression.4 The reason for this serious toxicity was that the mitomycin C was given on the schedule used for 5-Ÿuorouracil-daily injection for œve consecutive days-but it has cumulative and delayed toxicity to bone marrow. Bristol-Myers œnally received approval in 1974 for clinical use of mitomycin C based on a revised dosage schedule.5
