Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil in advanced gastric cancer refractory or intolerant to fluoropyrimidines, platinum, taxanes, and irinotecan

Gastric Cancer. 2018 Nov;21(6):1050-1057. doi: 10.1007/s10120-018-0825-y. Epub 2018 Apr 16.

Abstract

Background: Although nivolumab showed survival benefit in patients with advanced gastric cancer (AGC) progressing after standard chemotherapy, there is a lack of data regarding oxaliplatin-based chemotherapy in this clinical setting.

Methods: We retrospectively evaluated the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil as salvage treatment in patients with AGC refractory or intolerant to fluoropyrimidines, cisplatin, taxanes, and irinotecan.

Results: Overall, 50 patients treated between December 2009 and December 2013 were included in this analysis. The overall response rate (ORR) was 21.2% among 33 patients with measurable disease. The median time to treatment failure (TTF) and overall survival (OS) were 2.4 and 4.2 months. In multivariate analysis, factors associated with OS included poor performance status [hazard ratio (HR) 3.20; 95% confidence interval (CI) 1.55-6.60], shorter time from the start of first-line therapy (HR 2.20; 95% CI 1.18-4.12), and higher neutrophil/lymphocyte ratio value (HR 4.87; 95% CI 2.32-10.25). In patients (n = 35) with at most one risk factor, the ORR, median TTF, and OS were 26.1%, 3.6, and 6.7 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (30%), anemia (22%), febrile neutropenia (8%), and peripheral neuropathy (8%). Initial and subsequent dose reduction was performed in 18 (36%) and 23 (46%) patients. There was one treatment-related death caused by septic infection.

Conclusions: Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil has a potential activity and is tolerable for heavily treated AGC with appropriate dose modification and patient selection.

Keywords: Gastric cancer; Oxaliplatin; Prognostic factor; Salvage therapy.

Publication types

  • Clinical Trial

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Irinotecan / administration & dosage
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin / administration & dosage
  • Salvage Therapy / adverse effects
  • Salvage Therapy / methods*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • Cisplatin
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol