Phase II study of adozelesin in untreated metastatic breast cancer

Adozelesin is the first of a class of DNA-sequence-selective alkylating agents, the cyclopropa(c)pyrrolo(3,2-e)indol-4(5H)-ones (CPls), that have been shown to have of potent inhibitory properties of DNA synthesis. Based on preliminary data from phase I studies showing clinical activity in patients with breast cancer, we initiated a multicenter phase II study in untreated metastatic breast carcinoma. Adozelesin was administered at a starting dose of 150 microg/m2 as a single 10 min infusion per course, repeated every 4 weeks, for up to 1 year of treatment. It was planned that at least 25 patients should be accrued but the trial was stopped early because of slow accrual and lack of efficacy as demonstrated by the infrequency of objective responses. Seventeen patients were enrolled in this study, only 14 were evaluable, the following responses were observed: one partial response (7%), three stable diseases (22%) and 10 progressive diseases (71%). Myelosuppression was the most frequent adverse event; one patient died of pulmonary complications. We conclude that adozelesin has marginal efficacy in the treatment of metastatic breast cancer at the dosage and schedule used in this study.