Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603

J Clin Oncol. 2026 May 20;44(15):1395-1400. doi: 10.1200/JCO-25-01231. Epub 2026 Jan 21.

Abstract

JCOG0603 demonstrated improved disease-free survival (DFS) with adjuvant mFOLFOX6 after hepatectomy compared with hepatectomy alone in colorectal liver-only metastasis (CRLM), but the overall survival (OS) data were immature. Here, we report OS after long-term follow-up. Eligible patients with colorectal adenocarcinoma and an unlimited number of liver metastases were randomized to adjuvant mFOLFOX6 or hepatectomy alone. DFS was the primary endpoint, and OS was a secondary endpoint. Between March 2007 and January 2019, 151 and 149 patients were randomized to adjuvant chemotherapy and hepatectomy alone, respectively. At a median follow-up of 7.7 years for disease-free surviving patients, 54 (35.8%) and 51 (34.2%) patients had died in the respective arms, (hazard ratio [HR], 1.07 [95% CI, 0.73 to 1.57]). Five-year OS was 73.4% (95% CI, 65.5 to 79.7) and 80.1% (95% CI, 72.6 to 85.7) and 7-year OS was 69.4% (95% CI, 61.2 to 76.2) and 72.4% (95% CI, 64.2 to 79.1), respectively. One patient in the adjuvant chemotherapy arm possibly died of protocol treatment-related toxicity, and one in the hepatectomy-alone arm died of post-protocol treatment complications. Five-year DFS was respectively 49.7% (95% CI, 41.5 to 57.3) and 40.5% (95% CI, 32.5 to 48.3) in the adjuvant chemotherapy and hepatectomy-alone arms (HR, 0.72 [95% CI, 0.54 to 0.97]). Long-term OS did not differ with adjuvant mFOLFOX6 compared with hepatectomy alone in resectable CRLM. Adjuvant mFOLFOX6 may delay recurrence but did not improve long-term survival.

Publication types

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

MeSH terms

  • Adenocarcinoma* / secondary
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms* / mortality
  • Colorectal Neoplasms* / pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Hepatectomy* / adverse effects
  • Hepatectomy* / mortality
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / secondary
  • Liver Neoplasms* / surgery
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use

Substances

  • Leucovorin
  • Fluorouracil
  • Organoplatinum Compounds

Supplementary concepts

  • Folfox protocol