Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study

Cancer Commun (Lond). 2018 Jun 4;38(1):32. doi: 10.1186/s40880-018-0304-1.

Abstract

Background: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer.

Methods: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan-Meier methods.

Results: We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5-6.0 months) and 8.5 months (95% CI 5.6-11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred.

Conclusion: Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

Keywords: Attenuated FOLFIRINOX; Gemcitabine; Pancreatic cancer; Second-line.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Drug Combinations
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Gemcitabine
  • Humans
  • Irinotecan / administration & dosage
  • Irinotecan / adverse effects
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neutropenia / chemically induced
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / adverse effects
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / adverse effects
  • Pancreatic Neoplasms / drug therapy*
  • Prospective Studies
  • Salvage Therapy / adverse effects
  • Salvage Therapy / methods*

Substances

  • Drug Combinations
  • Organometallic Compounds
  • folfirinox
  • Oxaliplatin
  • Deoxycytidine
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Gemcitabine