O1-003 - Preliminary Safety Data from Randomized Phase II Study Comparing Dose-Escalated Weekly Paclitaxel Versus Standard-Dose Weekly Paclitaxel for Patients with Previously Treated Advanced Gastric Cancer

Abstract

ABSTRACT Background Recently, we studied the effects of neutropenia occurring during second-line chemotherapy with weekly paclitaxel in a retrospective analysis of 242 patients with advanced gastric cancer, and observed better survival among patients with neutropenia compared to patients without neutropenia (Shitara K, et al. Annals of Oncol. 2011). Therefore, we conducted a multi-institutional, open-label, randomized phase II trial comparing dose-escalated weekly paclitaxel with dose adjustments determined by degree of neutropenia versus standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer (protocol ID UMI04055). Patients and methods Patients with advanced or recurrent gastric cancer that progressed during one or more previous chemotherapy regimens were included. Ninety patients were randomized to a standard dose of weekly paclitaxel (80 mg/m2, Arm A) or an escalated dose of weekly paclitaxel (80 mg/m2 on day 1, 100 mg/m2 on day 8, and 120 mg/m2 on day 15 unless severe toxicity is observed, Arm B). The primary endpoint was overall survival. Secondary endpoints included objective response rate, disease control rate, progression-free survival, and adverse events. We present the preliminary safety data from the first 8 weeks. Results From September 2010 to November 2011, a total of 90 patients were enrolled at 13 institutions. One patient in Arm B did not receive paclitaxel. The dose of paclitaxel was escalated to 100 mg/m2 in 41 patients (91.1%) and then to 120 mg/m2 in 29 patients (64.4%) in Arm B. In the first 8 weeks, 25 (55.5%) patients in Arm A patients and 20 (46.7%) patients in Arm B required dose reduction or treatment delay. Frequencies of grade 1 or more neutropenia were 66.7% in Arm A and 86.4% in Arm B, and grade 3 or more neutropenia frequencies were 31.1% in Arm A and 38.6% in Arm B. Grade 1 or more sensory neuropathy frequencies were 55.6% in Arm A and 68.1% in Arm B. Two patients in Arm A and one patient in Arm B experienced febrile neutropenia. No treatment-related deaths occurred. Conclusions Preliminary safety data during the first 8 weeks of treatment indicate comparable compliance between the two arms, despite the substantial number of patients who underwent dose escalation. Disclosure All authors have declared no conflicts of interest.