The search for more active and less toxic mitomycin and etoposide analogs

Abstract

Mitomycin C has broad-spectrum activity, but clinical utility is limited by cumulative myelosuppression. VP-16 also has broad-spectrum activity and, although myelosuppression is the dose-limiting toxicity, unlike mitomycin C it is predictable and reversible. Using toxicity reduction as a target for analog selection with mitomycin C has not yet resulted in a more clinically effective agent. Another goal would be to look for more rapid recovery and reversibility of myelosuppression, or compounds with greater antitumor activity or a different antitumor profile. With VP-16, analog evaluation is in an early stage, but selection based upon increased activity not reduced toxicity appears to be the avenue of choice and has resulted in the preliminary identification of analogs which in initial studies have superior activity to the parent compound.