A phase I/II dose escalation trial of @entity14514 every 3 weeks in XXXX with @entity1149 ( @entity1149 ).

@entity1 @entity137 @entity6023 @entity21597 @entity5 @entity294 @entity1149 @entity1205 @entity1897 @entity902 @entity14514
UNASSIGNED: 7248 Background: @entity1 (pts) with newly diagnosed advanced @entity1149 usually receive a @entity902 -containing doublet. However, these regimens are associated with cumulative @entity137 (myelosuppression and @entity1897 ) and the vast majority of pts eventually relapse and die of their disease. Clearly, improved cytotoxic agents are needed for the treatment of advanced @entity1149 . @entity14514 , a novel @entity21597 , is a potent microtubule stabilizer that causes cell death and is active in a variety of @entity5 , including those that are resistant to @entity6023 . We conducted a phase I/II study to determine the maximum tolerated dose (MTD) and investigate the safety and efficacy of @entity14514 in pts with stage IIIB/IV @entity1149 who had relapsed after @entity902 -based therapy. METHODS: Pts who had received 1 prior @entity902 -containing regimen and did not have symptomatic brain metastases were enrolled. During the phase I study, dose escalation will follow the standard 3 + 3 design until the MTD is reached. Pts received @entity14514 at a starting dose of 6.5 mg/m(2) as a 5-min IV infusion once every 3 weeks with dose escalation in 0.5 mg/m(2) increments. During the phase II portion of the study, pts will be treated at the MTD until disease progression or unacceptable @entity137 occurs. RESULTS: To date, 9 pts (6 male, 3 female) have been enrolled into the phase I portion of the study. Eight of 9 pts had achieved a partial response or stable disease with prior therapy. The ninth pt had progressed while receiving @entity1205 plus @entity902 as first-line therapy. Median age was 61 years (range, 44 - 77), and median performance status was 1. Three pts were enrolled in cohort 1 (6.5 mg/m(2)), 3 in cohort 2 (7.0 mg/m(2)), and 3 in cohort 3 (7.5 mg/m(2)). Only 2 severe adverse events have been reported, including 1 grade 3 @entity294 responding to medication (cohort 1) and 1 grade 3 asthenia reversed in 5 days (cohort 3). All other adverse events were grade 1 or 2; no serious hematologic @entity137 were reported. The MTD has not been reached, and dose escalation continues. CONCLUSION: Preliminary results suggest that @entity14514 is generally well-tolerated in pts with advanced @entity1149 . Dose escalation continues and updated results will be presented. [Table: see text].
