Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial

Eur J Cancer. 2015 May;51(8):942-9. doi: 10.1016/j.ejca.2015.02.013. Epub 2015 Mar 25.

Abstract

Background: The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC.

Methods: In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety.

Results: Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications.

Conclusion: Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone.

Keywords: Colorectal neoplasms; Fluorouracil; Leucovorin; Oxaliplatin; Regorafenib; Safety; Survival rate; Treatment outcome.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Historically Controlled Study
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / adverse effects
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Phenylurea Compounds
  • Pyridines
  • regorafenib
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol