Ramdomized 3-armed phase III study of S-1 monotherapy versus S-1/CDDP (SP) versus 5-FU/CDDP (FP) in patients (pts) with advanced gastric cancer (AGC): SC-101 study

Abstract

4533 Background: SP has been widely used against AGC in Japan. To further evaluate the efficacy and safety for SP in Chinese, we conducted a 3-arm study to investigate superiority of SP to S-1 and FP in pts with AGC. The primary endpoint was response rate (RR) and secondary endpoints were time to treatment failure (TTF), overall survival (OS) and safety. Methods: Treatments with Arm A (S-1 montherapy: S-1 80 mg/m2/d, d1∼28, q6w); Arm B (SP: S-1 80 mg/m2/d, d1∼21, plus CDDP 60 mg/m2 iv d8, q5w); Arm C (FP: 5-FU 600 mg/m2/d, civ, plus CDDP 20 mg/m2/d, iv 30 minutes, d1∼d5, q4w) were continued until disease progression or unacceptable toxicities. Eligibility criteria included unresectable/recurrent AGC, age≥18 years, and no prior chemotherapy. With 60 pts per arm, the trial was designed to have 80% power to detect an improvement of Arm B in RR (2 sided significance level p=0.025). CMH test was applied to RR. Log-rank test and Kaplan-Meier estimation were applied to TTF and OS. Used IRC (Independent Review Committee) evaluation as RR results. Arm C patients could switch to S-1 after treatment failure. Results: From July 2005 to Oct 2006, 230 pts (Arm A/B/C, 80/76/74) were randomized. The FAS were 224 patients (Arm A/B/C, 77/74/73). Median age was 57/56.5/58 yrs. RR(%) of Arm A/B/C were 24.7/37.8/19.2. The RR of Arm B was superior to Arm C (CMH p=0.021, odd ratio: 0.387, 95%CI:0.177∼0.847). The MST (days) were 267 (95%CI:202–323)/433 (95%CI:365-)/309 (95%CI:238-) at the time of analysis (Jan 15, 2007) when 42% of pts were dead. The OS of Arm B was superior to Arm C (Log-rank p=0.038) and Arm A (Log-rank p<0.001). The TTF (days) were 126 (95%CI: 92–152)/159 (95%CI:146–220)/85 (95%CI:66–106). The TTF of Arm B was superior to Arm C (Log-rank p<0.001) and Arm A (Log-rank p=0.008). 41 pts in Arm C switched to S-1 with the RR 14.6%. The most common grade 3/4 toxicities in Arm A/B/C (%) were: anemia, 2.5/5.3/5.4; leucopenia, 1.3/13.2/9.5; neutropenia, 3.8/17.1/16.2; PLT decreased, 0/6.6/12.2; nausea, 0/2.6/5.4; vomiting, 1.3/6.6/12.2; diarrhea, 3.8/6.6/0. No new drug- related SAE was observed. Conclusions: Both S-1 and SP regimen were found to be effective and well tolerated. Furthermore SP could be one of the standard regimens in Chinese pts with AGC. No significant financial relationships to disclose.