Phase I study of combination therapy with S-1 and weekly docetaxel for advanced gastric cancer

Anticancer Res. 2007 Jul-Aug;27(4C):2657-65.

Abstract

Background: The primary objective of this study was to determine the maximum tolerated dose (MTD), the toxicity profile and the recommended dose (RD) for phase II of a combination of S-1 and weekly administration of docetaxel.

Patients and methods: Patients with histologically diagnosed recurrent or unresectable locally advanced gastric cancer were enrolled. A fixed oral dose of 80 mg/m2 S-1 was given for 3 weeks. Docetaxel was infused intravenously on day 1, 8 and 15, repeated every 5 weeks. A pharmacokinetic study was also performed.

Results: A total of 14 patients were enrolled. One dose-limiting toxicity (DLT) (grade 3 diarrhea with febrile neutropenia) occurred at level 2. DLTs occurred in 3/5 patients at level 3, (grade 3 stomatitis, with febrile neutropenia or continuous grade 4 neutropenia). The pharmacokinetic study suggested no drug interactions. Overall response and disease control rates were 20% and 80%, respectively. The response rate at the RD (level 2) was 50%. Overall survival was 9.4 months.

Conclusion: RD was level 2 (80 mg/m2 of S-1 for 3 weeks and 20 mg/m2 of docetaxel on day 1, 8 and 15, every 5 weeks). Dose intensities of S-1 and docetaxel were 48 mg/m2/week and 12 mg/m2/week, respectively. This regimen showed promising activity for advanced gastric cancer.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Docetaxel
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Oxonic Acid / pharmacokinetics
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Taxoids / pharmacokinetics
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Tegafur / pharmacokinetics

Substances

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