A randomized phase II study of S-1 versus capecitabine as first-line chemotherapy in elderly metastatic gastric cancer patients with or without poor performance status: clinical and pharmacogenetic results
This study investigated the efficacy and safety of S-1 versus capecitabine in elderly patients with metastatic gastric cancer (MGC), and examined the association between cytochrome P450 2A6 (CYP2A6) polymorphisms and treatment outcomes.Materials and methods
MGC patients 70–85 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0–2 or 65–70 years old with ECOG PS 2 were randomized to receive S-1 40 mg/m2, twice daily, or capecitabine 1250 mg/m2, twice daily, on days 1–14 every 3 weeks.Results
From May 2007 up to July 2010, 107 patients were enrolled. G3/4 neutropenia developed in 3.8% of each arm, and the most common G3/4 nonhematological toxicities were anorexia and fatigue. Vomiting and tearing were more frequent with S-1 and hand–foot syndrome with capecitabine. The primary endpoint, the overall response rate, was 26.4% (14/53, 95% confidence interval: 14.5–38.3%) in S-1 and 24.1% (13/54, 95% confidence interval: 12.7–35.5%) in capecitabine, both of which exceeded the null hypothesis response rate of 10%. The median time to progression (TTP; 3.2 vs. 3.4 months, P=0.813) and overall survival (OS; 8.5 vs. 10.3 months, P=0.691) were similar in both arms. CYP2A6 polymorphisms were associated with S-1 efficacy. In the S-1 arm only, patients with CYP2A6 variant/variant alleles had worse TTP and OS than those with wild/wild or wild/variant alleles, and in multivariate analysis, the CYP2A6 genotype was predictive for TTP and OS.Conclusion
Both S-1 and capecitabine were active and tolerable for elderly MGC patients. The CYP2A6 genotyping might guide treatment selection.