Phase I pharmacokinetic study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer

Oncology. 2009;76(5):311-4. doi: 10.1159/000209277. Epub 2009 Mar 20.

Abstract

Objectives: A dose-escalation study of weekly intraperitoneal paclitaxel (PTX) combined with S-1 and intravenous PTX was performed to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients.

Patients and methods: Nine gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered intravenously on days 1 and 8 at a fixed dose of 50 mg/m(2), and intraperitoneally with an initial dose of 20 mg/m(2), stepped up to 30 or 40 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day for 14 consecutive days, followed by 7 days of rest. A pharmacokinetic study of PTX was also performed.

Results: The MTD was determined to be 30 mg/m(2), as 2 of 3 patients developed dose-limiting toxicities, grade 3 febrile neutropenia and diarrhea. Therefore, the RD was determined to be 20 mg/m(2). The intraperitoneal and serum PTX concentration remained effective for over 72 and 48 h, respectively.

Conclusions: Combined chemotherapy of S-1 plus weekly intravenous and intraperitoneal PTX was shown to be a safe regimen that should be further explored in clinical trials.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Drug Combinations
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Intraperitoneal
  • Lymphatic Metastasis
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Oxonic Acid / administration & dosage
  • Paclitaxel / administration & dosage
  • Peritoneal Neoplasms / metabolism*
  • Peritoneal Neoplasms / secondary
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tegafur / administration & dosage
  • Tissue Distribution
  • Treatment Outcome

Substances

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