Outcomes of preoperative S-1 and docetaxel combination chemotherapy in patients with locally advanced gastric cancer

Cancer Chemother Pharmacol. 2019 Jun;83(6):1047-1055. doi: 10.1007/s00280-019-03813-6. Epub 2019 Mar 25.

Abstract

Purpose: The therapeutic outcomes of stage III gastric cancer patient receiving D2 gastrectomy and adjuvant chemotherapy remain unsatisfactory. To improve the long-term outcomes in this population, the combination of docetaxel and S-1 (DS) therapy can be expected to be a useful regimen as neoadjuvant chemotherapy (NAC). This study aimed to prospectively evaluate the efficacy of NAC-DS for clinical stage III gastric cancer.

Methods: Between January 2010 and December 2013, 26 patients were enrolled. Patients with clinical stage III gastric cancer received two courses of docetaxel 40 mg/m2 on day 1, 15 and S-1 40 mg/m2 bid orally on day 1-7, 15-21 every 4 weeks, followed by radical D2 gastrectomy. Short- and long-term outcomes were evaluated. This study was approved by the ethics committee of Yokohama City University, and was registered in the University Hospital Medical Information Network (UMIN) database (ID: 000011521).

Results: Of 26 patients, 24 (92.3%) patients completed two courses of NAC. After NAC-DS, Grade 3 neutropenia was observed in 5 (19.2%) patients including one patient with febrile neutropenia, anemia in 1 (3.8%) patient and diarrhea in 1 (3.8%) patient. All patients underwent R0 gastrectomy and pathological response was found in 15 (57.6%) patients. Postoperatively, Clavien-Dindo grade II complication occurred in 8 (30.7%) patients and no mortality was observed. The 5-year overall survival (OS) was 57.7%, median OS was 78.7 months and recurrence free survival (RFS) was 49.0%, median RFS was 45.4 months with 66.5 months median follow-up. Pathological response (HR = 0.091, 95% CI 0.011-0.730, p = 0.016) and > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for recurrence, > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for overall survival by multivariate analysis.

Conclusions: NAC-DS demonstrated acceptable toxicity with a high R0 resection rate in clinical stage III gastric cancer patients, especially in patients with good nutritional status. Further prospective study is warranted to compare the long-term outcomes between with and without NAC-DS.

Keywords: Docetaxel; Gastric cancer; Preoperative chemotherapy; S-1.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Disease-Free Survival
  • Docetaxel / administration & dosage
  • Drug Combinations
  • Female
  • Gastrectomy / methods*
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Oxonic Acid / administration & dosage
  • Prospective Studies
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Survival Rate
  • Tegafur / administration & dosage
  • Treatment Outcome

Substances

  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Docetaxel
  • Oxonic Acid