RANDOMIZED PHASE III STUDY OF IRINOTECAN (CPT-11) VERSUS WEEKLY PACLITAXEL (WPTX) FOR ADVANCED GASTRIC CANCER (AGC) REFRACTORY TO COMBINATION CHEMOTHERAPY (CT) OF FLUOROPYRIMIDINE PLUS PLATINUM (FP): WJOG4007 TRIAL

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Abstract

Background

A combination CT of FP has been regarded as the standard first-line treatment of AGC. Although two randomized trials showed a survival benefit of second-line CT (CPT-11 or docetaxel) compared with the best supportive care, no standard regimen has been established. In Japan, wPTX has been used more frequently than docetaxel as the second-line CT. The objective of this study was to compare CPT-11 with wPTX in patients with AGC refractory to FP.

Methods

Patients with AGC refractory to the first-line FP regimen were randomized 1:1 to either CPT-11 (150 mg/m2, q2w) or wPTX (80 mg/m2, days 1, 8, 15, q4w). The primary end point was overall survival (OS) and secondary end points were progression-free survival (PFS), overall response rate (ORR), adverse events and receiving rates of third-line CT.

Results

Between August 2007 and August 2010, 223 patients were enrolled; 112 patients were randomized to CPT-11 and 111 patients to wPTX. Baseline characteristics were well balanced between arms. Median OS was 8.4 months for CPT-11 and 9.5 months for wPTX (HR 1.132; 95% CI, 0.86–1.49; P = 0.38). Median PFS was 2.3 months for CPT-11 and 3.6 months for wPTX (HR 1.14; 95% CI, 0.88–1.49; P = 0.33). The ORR was 13.6% (12 of 88) for CPT-11 and 20.9% (19 of 91) for wPTX (P = 0.20). The most common grade 3/4 adverse events were neutropenia (39.1% for CPT-11 versus 28.7% for wPTX), anemia (30.0% versus 21.3%), anorexia (17.3% versus 7.4%) and fatigue (12.7% versus 6.5%). Four (4%) CPT-11 and three (3%) wPTX recipients died within 30 days after the last administration. Subsequent CT was carried out in 80 patients (71%) for CPT-11 and 97 patients (89%) for wPTX. Seventy-five patients (67%) in the CPT-11 group and 87 patients (80%) in the wPTX group received the crossover CT.

Conclusions

The WJOG4007 trial, the first phase III study comparing second-line CT regimens for AGC did not demonstrate the superiority of CPT-11 over wPTX. Thus, wPTX can be adopted as a control arm of future phase III trials of second-line CT for AGC.

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