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 Background Neutropenia during chemotherapy has been reported to be a predictor of better survival in patients with several types of cancers including gastric cancer. Therefore, we conduct a multi-institutional, randomized phase II trial comparing dose-escalated weekly paclitaxel dose adjustments determined by degree of neutropenia versus standard dose weekly paclitaxel for patients with previously treated advanced gastric cancer. Patients and methods Patients who had advanced or recurrent gastric cancer who showed disease progression during one or more previous chemotherapy regimens was included. A total of 90 patients were randomized to receive either a standard dose of weekly paclitaxel (80 mg/m2, Arm A) or an escalated dose of weekly paclitaxel (80 mg/m2 initially followed by 100 mg/m2 on day 8 and 120 mg/m2 on day 15, Arm B). The primary end point is overall survival. Secondary end points include objective response rate, disease control rate, progression-free survival and adverse events. We present the preliminary safety data during first 8 weeks. Results From September 2010 to November 2011, a total of 90 patients were enrolled from 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. Patients who required dose reduction or treatment delay during 8 weeks were 25 (55.5%) in Arm A and 21 (46.7%) in Arm B. The frequencies of grade 1 or more neutropenia were 66.7% in Arm A and 86.4% in Arm B, and grade 3/4 neutropenia were 31.1% in Arm A and 38.6% in Arm B. Grade 1 or more sensory neuropathy 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. Conclusions Preliminary safety data during 8 weeks indicate comparable compliance between the two arms despite substantial patients with dose escalation. The final efficacy results will be assessed in November 2012.