Phase II study of biweekly gemcitabine followed by oxaliplatin and simplified 48-h infusion of 5-fluorouracil/leucovorin (GOFL) in advanced pancreatic cancer

Cancer Chemother Pharmacol. 2009 Nov;64(6):1173-9. doi: 10.1007/s00280-009-0980-2. Epub 2009 Mar 25.

Abstract

Purpose: To evaluate the efficacy and safety profile of a triplet regimen consisting of gemcitabine, oxaliplatin, and infusional fluorouracil and leucovorin (LV) in advanced pancreatic carcinoma (APC).

Patients and methods: Chemotherapy-naïve patients with histo-/cytologically proven unresectable APC, and bi-dimensionally measurable diseases were eligible. Treatment consisted of fixed-dose rate (10 mg/m(2)/min) infusion of 800 mg/m(2) gemcitabine followed by 2-h infusion of 85 mg/m(2) oxaliplatin and then 48-h infusion of fluorouracil and LV (3,000 and 300 mg/m(2), respectively) every 2 weeks (the GOFL regimen). The primary end-point was objective response rate.

Results: Forty-five patients were enrolled and received a median of seven [95% confidence interval (CI) 6.4-8.8] cycles of treatment. On intent-to-treat analysis, the overall response and disease-control rates were 33.3% (95% CI 21.4-48.0%) and 68.9% (95% CI 54.8-83.0%), respectively. Clinical benefit response was observed in 46.2% of initially symptomatic patients. The median time-to-tumor progression and overall survival were 5.1 (95% CI 4.0-6.3) months and 8.7 (95% CI, 6.1-11.3) months, respectively. Major grade 3-4 toxicities were neutropenia (28.9%, with 4.4% complicated with fever), peripheral sensory neuropathy (15.6%), nausea/vomiting (13.3%), and diarrhea (6.7%).

Conclusions: The triplet regimen is feasible and exhibits promising activity against APC, deserving further exploration.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use*
  • Gemcitabine
  • Humans
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy*
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Leucovorin
  • Fluorouracil
  • Gemcitabine