Gastric Cancer. 2016 Apr;19(2):586-596. doi: 10.1007/s10120-015-0490-3. Epub 2015 Apr 8.

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

Kim YW, Kim MJ, Ryu KW, Lim HS, Lee JH, Kong SY, Lee JS, Choi IJ, Kim CG, Lee JY, Cho SJ, Kook MC, Park YI, Kim SK, Park SR.

Abstract

BACKGROUND:

We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in   locally advancedgastric 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. Clinicaltumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.

KEYWORDS:

CYP2A6 genotype; Docetaxel; Gastric cancer; Perioperative chemotherapy; S-1

PMID:

25851942

DOI:

10.1007/s10120-015-0490-3