Randomized phase III study of S-1 alone versus S-1 plus docetaxel (DOC) in the treatment for advanced gastric cancer (AGC): The START trial.

Abstract

7 Background: S-1/cisplatin is regarded as one of the standard regimens in Japan by the SPIRITS trial, but cisplatin needs in-hospital treatment for hydration. Phase II data of S-1/DOC showed long survival by outpatient basis. Then we hypothesized that S-1/DOC can be the standard regimen for AGC as outpatient basis. Methods: This is a prospective, multinational randomized phase III study in pts with AGC. Arm A: pts receive S-1 (40mg/m2) twice daily 14 days followed by 7 days rest plus DOC (40 mg/m2) iv on day 1. Arm B: pts receive S-1 28days followed by 14 days rest. Eligibility criteria included measurable/nonmeasurable AGC, age 20–79 and no prior chemotherapy. Primaryendpoint was OS, secondary endpoints were TTP, RR and safety. Based on planned sample size of 628 pts, the trial was designed tohave 90% power to detect an improvement in OS from 300 to 400 days. The accrual period was 3 years with 2 years follow up. Results: 639 pts (Arm A/B, 316/323) were registered and the eligible pts were 635 (314/321).The MST for Arm A was 386 and for Arm B was 327days. The OS for Arm A was not superior to Arm B (log-rank p = 0.1595, HR: 0.88). The TTP for Arm A was 160 and for Arm B was 126 days. The TTP for Arm A was significantly superior to Arm B (log-rank p < 0.0003, HR: 0.74). RR of Arm A was significantly higher than Arm B (36.0%/ 24.4%, p = 0.01). By subset analysis of OS in pre-stratified nonmeasurable AGC, the MST for Arm A was significantly superior to for Arm B (523/335, log-lank p = 0.018). Most common grade 3/4 toxicities were: neutropenia, 31.4% vs. 4.4%; leucopenia, 22.1% vs. 2.5% and anorexia; 15.4% vs. 12.1%. Conclusions: The combination ofS-1/DOC did not meet primary endpoint of OS, but of OS in nonmeasurable group and TTP of the S-1/DOC was significantly superior to that of the S-1 alone. We supposed that recent development of the second-line chemotherapy was influenced to our results. This regimen can be regarded as one of the standard treatments for AGC as outpatient basis. [Table: see text]