A phase I study of TPI 287, a third generation taxane, administered every 21 days in patients with advanced cancer

2569 Background: TPI 287 is a third generation taxane engineered to overcome multi-drug resistance and to bind to mutant tubulin. In preclinical studies, TPI 287 suppressed the growth of multiple human tumor xenografts in nude mice, including xenografts that expressed mdr- 1 and that 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 patients (pts) with advanced neoplasms. 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. DLT was defined as Gr 4 heme toxicity lasting 7 days; febrile neutropenia, Gr 3 thrombocytopenia with bleeding, Gr 3 elevation of transaminases lasting 7 days or any other Gr 3/4 toxicity other than nausea or vomiting. Results: 14 pts (M:F 5:9, med...