Adjuvant chemotherapy after resection of colorectal liver metastases in patients at high risk of hepatic recurrence: a comparative study between hepatic arterial infusion of oxaliplatin and modern systemic chemotherapy

Ann Surg. 2013 Jan;257(1):114-20. doi: 10.1097/SLA.0b013e31827b9005.

Abstract

Introduction: After curatively intended surgery for colorectal liver metastases, liver recurrences occur in more than 60% of patients, despite the administration of adjuvant systemic chemotherapy. The aim of this study was to assess the benefit of combined adjuvant hepatic arterial infusion (HAI) and intravenous (IV) 5-FU compared with standard modern adjuvant IV chemotherapy in patients at high risk of hepatic recurrence.

Patients and methods: From January 2000 to December 2009, 98 patients, who had undergone curative resection of at least 4 colorectal liver metastases, were selected from a prospective database. Among them, 44 (45%) had received postoperative HAI combined with systemic 5-FU (HAI group) and 54 (55%) had received "modern" systemic chemotherapy (IV group).

Results: The 2 groups were similar in terms of age, sex, the stage of the primary, and the administration of preoperative chemotherapy. The median number of HAI cycles received per patient was 7 [range, 1-12]. Twenty-nine patients (66%) had received at least 6 cycles of HAI oxaliplatin, and 22 patients (50%) had received the full planned treatment. For the remaining 22 patients (50%), HAI chemotherapy had been discontinued because of toxicity (n = 8), HAI catheter dysfunction (n = 6), an early recurrence (n = 6), and patient's refusal (n = 2). After a median follow-up of 60 months (51-81 months), 3-year overall survival was slightly higher in the HAI group (75% vs 62%, P = 0.17). Three-year disease-free survival was significantly longer in patients in the HAI group than those in the IV group (33% vs 5%, P < 0.0001). In the multivariate analysis, adjuvant HAI chemotherapy and an R0 resection margin status were the only independent predictive factors for prolonged disease-free survival.

Conclusions: Postoperative HAI oxaliplatin combined with systemic chemotherapy after curatively intended surgery of colorectal liver metastases is feasible and may significantly improve disease-free survival of patients at high risk of hepatic recurrence compared with adjuvant modern systemic chemotherapy alone. These results should be confirmed in a randomized study.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / pathology*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Hepatectomy*
  • Humans
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Irinotecan
  • Leucovorin / administration & dosage
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / prevention & control*
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Camptothecin