A Phase I and Pharmacokinetic Study of BAY59: A Novel Taxane

Purpose: To determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLT) and the pharmacokinetics of BAY59, a novel taxane given as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory solid tumors. Experimental Design: Initially, 15 patients with previously treated (median of 4 prior chemotherapy regimens) refractory cancers, but with normal marrow, hepatic and renal function were treated with BAY59 at doses of 15, 30, 50, 75 and 100 mg/m 2 using a standard dose escalation design. Subsequently, 11 patients were treated, 5 at 90 mg/m 2 and 6 who had had prior oxaliplatin at 75 mg/m 2 . Results: At 75 mg/m 2 , grade 4 neutropenia was noted in 2/6 patients, of whom 1 had grade 4 neutropenia lasting more than 5 days (DLT). At 100 mg/m 2 , 2/2 patients had febrile neutropenia, with 1 fatality. At 90 mg/m 2 , 2/5 patients had DLTs, including grade 3 neuropathy, severe lower extremity pain, dehydration and grade 4 neutropenia. The MTD was determined to be 75 mg/m 2 . A cohort of 6 patients, previously exposed to oxaliplatin, were enrolled at the MTD to evaluate the incidence of neurotoxicity. While DLTs (grade 3 arthralgia, grade 4 neutropenia) were noted in 3/6 patients, there was no increase in the incidence of neurotoxicity. There were no responses. Pharmacokinetics of BAY59 was linear over the doses studied, with a median terminal half-life of 21 h. Conclusions: The recommended phase II dose for BAY59 is 75 mg/m 2 .