A phase II pilot study of KW-2189 in patients with advanced renal cell carcinoma

Background: KW-2189 is a semi-synthetic, water-soluble analog of duocarmyci n B-2, a new class of potent antitumor antibiotics produced by streptomyces , with improved in vitro antitumor potency. Patients and methods: Forty pat ients with pathologically confirmed metastatic renal cell carcinoma were tr eated in this multicenter, open-label phase II trial. All patients received 0.4 mg/m(2) KW-2189 as an IV infusion for Cycle 1. Cycles were repeated ev ery 5 to 6 weeks with escalations to 0.5 mg/m(2) in the absence of signific ant toxicity or disease progression. Results: No patient had an objective r esponse. The most common drug-related toxicity was hematological-delayed ne utropenia and thrombocytopenia, with recovery by week 6. Non-hematologic to xicity consisted of mild to moderate fatigue, nausea and vomiting, and anor exia that was generally manageable. Conclusions: KW-2189 in this dose and s chedule has a predictable safety profile of reversible myelosuppression. No activity in metastatic renal cell carcinoma was demonstrated.