Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer

Eur J Cancer. 2016 Nov;68:163-172. doi: 10.1016/j.ejca.2016.09.011. Epub 2016 Oct 18.

Abstract

Background: Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m2) and triplet hepatic artery infusion (HAI) within European trial OPTILIV.

Methods: Irinotecan (180 mg/m2), 5-fluorouracil (2800 mg/m2) and oxaliplatin (85 mg/m2) were given as chronomodulated or conventional delivery. Patients were retrospectively categorised as early responders (complete or partial RECIST response after three courses) or non-early responders (late or no response). Prognostic factors were determined using multivariate logistic or Cox regression models.

Results: Response was assessed in 57 of 64 registered patients (89%), who had previously received one to three prior systemic chemotherapy protocols. An early response occurred at 6 weeks in 16 patients (28%; 9 men, 7 women), aged 33-76 years, with a median of 12 liver metastases (LMs) (2-50), involving five segments (1-8). Ten patients had a late response, and 31 patients had no response. Grade 3-4 fatigue selectively occurred in the non-early responders (0% versus 26%; p = 0.024). Early tumour response was jointly predicted by chronomodulation-odds ratio (OR): 6.0 (1.2-29.8; p = 0.029)-and LM diameter ≤57 mm-OR: 5.3 (1.1-25.0; p = 0.033). Early tumour response predicted for both R0-R1 liver resection-OR: 11.8 (1.4-100.2; p = 0.024) and overall survival-hazard ratio: 0.39 (0.17-0.88; p = 0.023) in multivariate analyses.

Conclusions: Early tumour response on triplet HAI and systemic cetuximab predicted for complete macroscopic liver resection and prolonged survival for LM-CRC patients within a multicenter conversion-to-resection medicosurgical strategy. Confirmation is warranted for early response on HAI to guide decision making. Protocol numbers: EUDRACT 2007-004632-24 NCT00852228.

Keywords: Colorectal cancer; Early tumour response; Hepatic artery infusion; Liver metastases; Triplet chemotherapy.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cetuximab / administration & dosage
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Fatigue / chemically induced
  • Female
  • Fluorouracil / administration & dosage
  • Hepatic Artery
  • Humans
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Irinotecan
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Proportional Hazards Models
  • Retrospective Studies
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • Cetuximab
  • Fluorouracil
  • Camptothecin

Associated data

  • ClinicalTrials.gov/NCT00852228
  • EudraCT/2007-004632-24