PURPOSE: The @entity21597 are a novel class of nontaxane microtubule-stabilizing agents. @entity19878 is a semisynthetic analog of the natural product @entity14514 . We conducted a phase I study administering @entity19878 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. @entity1 AND METHODS: Twenty-one @entity1 received @entity19878 without filgrastim in the first cycle. An additional six @entity1 were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 @entity1 had received prior @entity1311 , @entity1205 , or both. RESULTS: One hundred seven cycles were administered to 27 @entity1 . The maximum-tolerated dose was 6 mg/m2 of @entity19878 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting @entity137 at a dose of 8 mg/m2/d was @entity1398 with or without filgrastim support. Nonhematologic grade 3 @entity137 included fatigue (seven cycles), @entity3136 (two cycles), and @entity448 (one cycle). The mean terminal half-life of @entity19878 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in @entity1 with breast, cervical, and @entity5702 . Reductions in CA-125 levels were noted in @entity1 with @entity43 . CONCLUSION: The recommended phase II dose of @entity19878 on the daily schedule for 5 days is 6 mg/m2/d. @entity1398 was dose limiting, but higher doses were tolerated by a large fraction of @entity1 with filgrastim support. @entity1897 was mild, even after multiple cycles of therapy, and was not dose limiting.

Phase I trial and pharmacokinetic study of XXXX , an @entity14514 analog, administered intravenously on a daily schedule for five days.

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian cancer'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'toxicities'] @entity3136 :: ('MESH:D013280', 'Disease') :: ['stomatitis'] @entity21597 :: ('MESH:D034261', 'Chemical') :: ['epothilones'] @entity19878 :: ('MESH:C430592', 'Chemical') :: ['BMS-247550'] @entity1311 :: ('MESH:D017239', 'Chemical') :: ['paclitaxel'] @entity448 :: ('MESH:D000855', 'Disease') :: ['anorexia'] @entity1897 :: ('MESH:D010523', 'Disease') :: ['Peripheral neuropathy'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['Neutropenia', 'neutropenia'] @entity5702 :: ('MESH:D018295', 'Disease') :: ['basal cell cancer'] @entity1205 :: ('MESH:C067311', 'Chemical') :: ['docetaxel'] @entity14514 :: ('MESH:C093788', 'Chemical') :: ['epothilone B']
@entity19878 :: (MESH:C430592,Chemical) :: ['BMS-247550']
