SCHEDULE-DEPENDENT PACLITAXEL TOLERANCE ACTIVITY - DATA FROM A 7 DAY INFUSION PHASE-I STUDY WITH PHARMACOKINETICS IN PACLITAXEL REFRACTORY OVARIAN-CANCER/

Our objective was to determine the maximum tolerated dose (MTD) of pac litaxel when given as a 7 day continuous i.v. infusion, repeated every 3 weeks, and to evaluate the toxicity and the efficacy of such a sche dule of administration as a salvage treatment in ovarian cancer patien ts pretreated and refractory to 3 or 24 h paclitaxel. Thirteen women w ere enrolled in this phase I trial, Four dose levels ranging from 105 to 157.5 mg/m(2)/cycle were explored, Two of four patients experienced dose-limiting febrile neutropenia at the dose of 157.5 mg/m(2), No ob jective response was observed, although three patients experienced dis ease stabilization (five to six cycles), with regression of disease sy mptoms, two of them having sustained 50% or greater decrease in CA 125 , We conclude that the MTD in this population was paclitaxel 140 mg/m( 2)/7 days, Schedule-dependent mechanisms of resistance to paclitaxel c ould not be demonstrated in this clinical setting of heavily pretreate d ovarian cancer patients.