A phase I study of TPI 287, a novel taxane, administered every 21 days in patients (pts) with advanced cancer

13510 Background: TPI 287 is a novel taxane engineered to overcome multi-drug resistance. In preclinical studies, TPI 287 suppressed the growth of multiple human tumor xenografts in nude mice, including xenografts that expressed mdr-1 and were resistant to other taxanes. The safety and tolerability of TPI 287 when administered every 21 days was examined in this Phase 1 dose escalation study in pts with advanced cancers. Methods: TPI 287 was administered over 1 hour every 21 days in ascending doses to groups of 3 pts. Treatment cohorts were expanded to 6 pts in the face of dose-limiting toxicity (DLT); pts could remain on study until the development of progressive disease or an intolerable adverse event. The maximum tolerated dose (MTD) was defined as the dose at which < 2/3 of pts experienced DLT. Results: 21 pts (M:F 5:9, median age 58.5, range 49 - 77) were enrolled in 5 dose levels ranging from 56 - 185 mg/m2. Pts’ cancers included colorectal (7 pts), pancreatic (2), NSCLC (2), breast (2) and one each ...