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.
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.
