Efficacy of patupilone in advanced local or metastatic gastric cancer: A phase IIa trial

Abstract

4069 Background: Although the use of taxanes has produced encouraging response rates in patients with advanced local or metastatic gastric cancer, outcomes remain unsatisfactory. Patupilone (EPO906; epothilone B), a novel microtubule stabilizer, has demonstrated anti-tumor activity against a broad range of tumors in vitro and in animal models. The present trial evaluated the efficacy of patupilone in patients with locally advanced or metastatic gastric cancer. Methods: Patients with confirmed gastric adenocarcinoma (defined by RECIST) received patupilone 2.5 mg/m2/wk by single 5- to 7-minute IV infusion for 3 weeks, followed by 1 week off (4-week cycle). Additional inclusion criteria: WHO performance status ≤2, age ≥18 years, life expectancy ≥3 months, and no major hematologic, renal, or hepatic impairment. The primary objective of this open-label, single-arm, 2-stage, multicenter study was to determine the objective response rate (using RECIST) of treatment with patupilone in this population. Results: All 22 patients enrolled were evaluable. Mean age was 61.1 years, 63.6% were men, and 72.7% were oriental. Of 18 patients (81.8%) who completed the study, 10 (45.5%) had disease progression and 8 (36.4%) died from the disease; of 4 discontinuations, 3 were due to adverse events (AEs) and 1 to abnormal alkaline phosphatase. Overall response: 2 patients had partial responses, 6 disease stabilization, 12 disease progression, and 2 unknown. The duration of response in the 2 partial responders was 176 and 113+ days, with the latter censored at 113 days. The most frequently reported AEs were diarrhea (n = 18), nausea (n = 14), vomiting (n = 13), abdominal pain (n = 10), and fatigue (n = 10). Of these AEs, 9 were grade 3 (4 diarrhea, 3 vomiting, 1 nausea, and 1 fatigue) and 2 were grade 4 (1 nausea and 1 vomiting). Grade 4 AEs also included 1 gastric outlet obstruction and 1 dehydration. Conclusions: Patupilone resulted in an overall tumor response/disease stabilization rate of 36.4%, was well tolerated, and may prove to be a viable alternative to taxane treatment in advanced local/metastatic gastric cancer. [Table: see text]