A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival.

Background: We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome.

Methods: Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system] received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2) twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1.

Results: From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and worse survival than those with wild/wild or wild/variant genotypes.

Conclusion: Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.