A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases

Clin Colorectal Cancer. 2020 Sep;19(3):e140-e150. doi: 10.1016/j.clcc.2020.03.004. Epub 2020 Apr 2.

Abstract

Introduction: Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear.

Material and methods: Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test.

Results: The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy.

Conclusions: In patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.

Keywords: Bevacizumab; Liver resection; Metastatic colorectal cancer; Perioperative chemotherapy; Resectable.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Carcinoembryonic Antigen / blood
  • Chemotherapy, Adjuvant / methods
  • Chemotherapy, Adjuvant / statistics & numerical data
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Hepatectomy / adverse effects
  • Humans
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / blood
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoadjuvant Therapy / statistics & numerical data*
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Perioperative Period / statistics & numerical data
  • Postoperative Complications / epidemiology
  • Postoperative Complications / etiology
  • Progression-Free Survival
  • Prospective Studies
  • Tomography, X-Ray Computed

Substances

  • Carcinoembryonic Antigen
  • Organoplatinum Compounds
  • Bevacizumab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol