Phase I and Pharmacokinetic Study of Irofulven, a Novel Mushroom-Derived Cytotoxin, Administered for Five Consecutive Days Every Four Weeks in Patients With Advanced Solid Malignancies

摘要: PURPOSE: To evaluate the toxicity and pharmacologic behavior of novel mushroom-derived cytotoxin irofulven administered as a 5-minute intravenous (IV) infusion daily for 5 days every 4 weeks to patients with advanced solid malignancies. PATIENTS AND METHODS: In this phase I trial, 46 were treated doses ranging from 1.0 17.69 mg/m2 IV (two received 1-hour infusion) weeks. The modified continual reassessment method was used dose escalation. Pharmacokinetic studies performed on 1 characterize plasma disposition irofulven. RESULTS: Forty-six 92 courses dose-limiting toxicities schedule myelosuppression renal dysfunction. At 14.15-mg/m2 level, dysfunction resembling tubular acidosis occurred in four 10 ameliorated by prophylactic hydration. 17.69-mg/m2 level not tolerated bec...