Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3)

Eur J Cancer. 2021 Nov:157:21-30. doi: 10.1016/j.ejca.2021.08.002. Epub 2021 Aug 28.

Abstract

Background: The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status.

Patients and methods: Eighty mPAC patients (age, 19-75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1-2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1-28 every 6 weeks.

Results: Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p < .001). The median overall survival rates were 9.2 and 4.9 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted HR: .4; 95% CI: .2-.7; p = .002). Grade 3-4 adverse events occurred in 56% and 17% of the patients in the mFOLFIRINOX and S-1 groups, respectively (p < .001).

Conclusion: Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.

Keywords: Gemcitabine; Modified FOLFIRINOX; Pancreatic neoplasms; Randomised controlled trial; S-1; Second-line chemotherapy.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Drug Combinations
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Gemcitabine
  • Humans
  • Irinotecan / adverse effects
  • Irinotecan / therapeutic use
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxaliplatin / adverse effects
  • Oxaliplatin / therapeutic use
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Quality of Life
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*

Substances

  • Drug Combinations
  • folfirinox
  • Oxaliplatin
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Gemcitabine