Prospective phase II study of neoadjuvant FOLFOX6 plus cetuximab in patients with colorectal cancer and unresectable liver-only metastasis

Cancer Chemother Pharmacol. 2013 Jul;72(1):223-30. doi: 10.1007/s00280-013-2190-1. Epub 2013 May 21.

Abstract

Purpose: Liver resection may offer the only chance of cure in patients with colorectal cancer with liver metastases. In the unresectable cases, neoadjuvant chemotherapy could render curability if resectability could be achieved.

Methods: Newly diagnosed K-RAS wild-type colorectal cancer patients with unresectable liver-only metastases were treated with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) plus cetuximab every 2 weeks for a maximum of 12 cycles. Clinical response was evaluated every 6 weeks, and surgery was performed at the physician's discretion in patients with sufficient tumor shrinkage, followed by chemotherapy with the same regimen, to complete a total of 12 cycles. The primary endpoint was an overall R0 resection rate.

Results: Between July 2008 and December 2009, 73 patients were registered from 11 Korean centers. Among 53 (73 %) patients who showed at least partial response, surgery with curative intent was attempted in 36 (49 %) patients. Intention-to-treat analysis revealed a R0 resection rate of 27 % (20/73) including 8 patients whose unresectable liver metastases were successfully treated with radiofrequency ablation (RFA). The most common grade 3 and 4 toxicity was neutropenia (50/462 cycles, 10.7 %). Median time to progression (TTP) was 9.8 months (range 0.5-31.8) in all patients, but we observed TTP of 14.1 months (range 1.3 to -30.8) in patients who received R0 resection and RFA + R0 resection.

Conclusions: Neoadjuvant chemotherapy with FOLFOX6 plus cetuximab showed high response rates and increased the resectability in colorectal patients with non-resectable liver-only metastases.

Publication types

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

MeSH terms

  • Ablation Techniques
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Humans
  • Intention to Treat Analysis
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Neutropenia / chemically induced
  • Neutropenia / physiopathology
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • Severity of Illness Index
  • Tumor Burden / drug effects
  • ras Proteins / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • KRAS protein, human
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol