O1-13-1RANDOMIZED PHASE II STUDY OF CPT-11 VS PTX; +/- S1 IN ADVANCED GASTRIC CANCER REFRACTORY TO S1 OR S1 + PLATINUM(OGSG0701)

Abstract Background: In Japan, S1 + platinum (SP) is recommended for advanced gastric cancer (AGC) patients as first-line setting, and S1 monotherapy is suggested for frail AGC patients or adjuvant setting. However, taxane or CPT-11 were often employed as second-line treatment for the patients who were resistant to S1-containing regimen. A retrospective analysis has reported that S1 combination chemotherapy extended overall survival as second-line treatment for AGC that was resistant to first-line S1-based chemotherapy. Methods: Patients with AGC who confirmed disease progression by imaging after the first-line therapy with S1 or SP were randomized in four groups. Treatment groups were divided as follows; CPT-11 alone (Group A), weekly paclitaxel (Group B), CPT-11 plus S1 (Group C1) and PTX plus S1 (Group C2). Primary endpoint was overall survival (OS), and secondary endpoints were progression free survival (PFS), response rate and safety. Sample size was set at 100 to 120 to achieve 2 months improvement of OS by using CPT-11 or by adding S1 with approximately 80% probability of the correct selection. Results: From July 2008 to March 2012, 127 patients were enrolled. The OS was 11.3/11.3/14.6/10.5 months(M) (Group A/B/C1/C2), 11.8M in Group A + C1 and 11.1M in Group B + C2 (p = 0.922, HR: 0.981 [0.679-1.419]), 11.3M in Group A + B and 11.1M in Group C1 + C2 (p = 0.808, HR: 0.952 [0.643-1.412]), respectively. The PFS was 3.0/4.4/3.8/3.5M (Group A/B/C1/C2), 3.6M in Group A + C1 and 4.1M in Group B + C2 (p = 0.035, HR:0.674 [0.468-0.972]) 3.7M in Group A + B and 3.7M in Group C1 + C2 (p = 0.931, HR: 1.017 [0.643-1.412]). Major Grade 3/4 toxicity (Group A/B/C1/C2, %), was leukopenia (12/7/5/0), neutropenia (29/16/24/24), nausea (7/2/10/5), diarrhea (5/0/10/0), and fatigue (5/2/10/5). There was one treatment-related death in Group A. Conclusions: From our results, we do not recommend consecutive use of S1 but CPT-11 or PTX monotherapy as second-line treatment in AGC patients who are refractory to S1 or SP.