Phase I and pharmacokinetic study of KRN8602 alone and with filgrastim in patients with advanced cancer

Abstract

Purpose: To determine the recommended dose, toxicity profile, and pharmacokinetics of KRN8602 (MX2-hydrochloride), a novel morpholino anthracycline with potent cytotoxicity against anthracycline-sensitive and resistant experimental tumors in vitro and in viva. Patients and Methods: KRN8602 was administered alone in increasing closes to patients with advanced cancer or high-grade gliomas until dose-limiting toxicity (DLT) was observed in three or more of five patients treated in a dose level. Because neutropenia was dose limiting, further escalation was investigated with filgrastim support. Results: Fifty-six assessable patients completed at least one cycle of chemotherapy. The recommended do..