Gemcitabine (GEM) plus oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX-4) in patients with advanced gastric cancer

Cancer Chemother Pharmacol. 2005 Dec;56(6):563-8. doi: 10.1007/s00280-005-1024-1. Epub 2005 Jul 23.

Abstract

Background and aims: oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM+FOLFOX-4 regimen in patients with metastatic gastric cancer.

Methods: we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37-78), who received bi-weekly treatment with GEM (1,000 mg/m2 on day 1), levo-FA (100 mg/m2 on days 1 and 2), a 5-FU (400 mg/m2) bolus injection followed by 22-h continuous infusion (800 mg/m2) on days 1 and 2, and oxaliplatin 85 mg/m2 in a 4-6 h intravenous (i.v.) infusion before the second FUFA administration on day 2.

Results: the most frequent side effect was grade 1-2 hematological toxicity and late sensorial neurotoxicity. Two patients developed hypersensitivity to oxaliplatin while another developed an aseptic eosinophilic pneumonitis. Two patients refused to continue the treatment after two cycles of chemotherapy and were lost at the follow-up. Among the remaining 34 patients four achieved a complete response, 15 a partial response, 12 had a stable disease and three progressed.

Conclusions: these results may grant the rationale to evaluate this multi-drug combination in randomized phase III trials in advanced gastric cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil / administration & dosage
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / pathology
  • Gemcitabine
  • Hematologic Diseases / chemically induced
  • Hematologic Diseases / pathology
  • Humans
  • Infusions, Intravenous
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology
  • Organoplatinum Compounds / administration & dosage
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Rate

Substances

  • Antimetabolites, Antineoplastic
  • Organoplatinum Compounds
  • Deoxycytidine
  • Leucovorin
  • Fluorouracil
  • Gemcitabine

Supplementary concepts

  • Folfox protocol