Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma

Pancreas. 2013 Nov;42(8):1311-5. doi: 10.1097/MPA.0b013e31829e2006.

Abstract

Objectives: FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, and irinotecan) as compared with gemcitabine in pancreatic cancer (PC) has superior activity and increased toxicity. The bolus 5-FU contributes to the toxicity. We hypothesized that the elimination of bolus 5-FU and use of hematopoietic growth factor will improve the safety profile without compromising the activity of FOLFIRINOX.

Methods: Sixty patients with PC treated with modified FOLFIRINOX (no bolus 5-FU) were reviewed. Patients were divided into metastatic or nonmetastatic (locally advanced or borderline resectable) disease. Toxicity, response rate, progression-free survival, and overall survival were evaluated.

Results: Nonmetastatic and metastatic disease were present in 24 (40%) and 36 (60%) patients, respectively. The incidence of grade 4 neutropenia, grade 3/4 diarrhea, and fatigue were 3%, 13%, and 13%, respectively. Response rate was 30%. The median progression-free survival for nonmetastatic disease was 13.7 months (95% confidence interval [CI], 9.6-24.6 months), and that for metastatic disease was 8.5 months (95% CI, 3.7-11.0 months), respectively. The median overall survival for nonmetastatic disease was 17.8 months (95% CI, 9.9 months to not estimable), and that for metastatic disease was and 9.0 months (95% CI, 7.1 months to not estimable), respectively.

Conclusions: Modified FOLFIRINOX has an improved safety profile with maintained efficacy in metastatic PC. Modified FOLFIRINOX has promising activity in nonmetastatic disease.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CA-19-9 Antigen / metabolism
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Fatigue / chemically induced
  • Female
  • Filgrastim
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Humans
  • Irinotecan
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Polyethylene Glycols
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Retrospective Studies
  • Treatment Outcome

Substances

  • CA-19-9 Antigen
  • Organoplatinum Compounds
  • Recombinant Proteins
  • Oxaliplatin
  • Granulocyte Colony-Stimulating Factor
  • pegfilgrastim
  • Polyethylene Glycols
  • Irinotecan
  • Filgrastim
  • Leucovorin
  • Fluorouracil
  • Camptothecin