Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin

Ann Surg Oncol. 2014 Jun;21(6):1792-800. doi: 10.1245/s10434-013-3442-3. Epub 2013 Dec 15.

Abstract

Background: Patients with stage IV colorectal cancer and peritoneal carcinomatosis are increasingly treated with curative intent and perioperative systemic chemotherapy combined with targeted therapy. The aim of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin.

Methods: From 2004 to 2010, in three referral centers, 182 patients with colorectal carcinomatosis were treated with complete cytoreduction followed by HIPEC after either preoperative systemic chemotherapy alone or in combination with bevacizumab. Because there was no control on treatment allocation, propensity score methods were used to control for this bias.

Results: The median time from discontinuation of bevacizumab to HIPEC was 7 weeks (range 6-10 weeks). Major morbidity was greater in the bevacizumab group (34 vs. 19 %, p = 0.020). Nine patients died postoperatively, 5 (6.2 %) in the bevacizumab group (n = 80) and 4 (3.9 %) in the group treated with chemotherapy alone (n = 102) (p = 0.130). The rate of digestive fistulas was greater in the bevacizumab group, although not statistically significant (18 vs. 10 %, p = 0.300). The effect of bevacizumab on major morbidity (including death) was found to be statistically significant (odds ratio 2.28, 95 % confidence interval 1.05-4.95) (p = 0.04).

Conclusions: Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for colorectal carcinomatosis is associated with twofold increased morbidity. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.

MeSH terms

  • Abdominal Abscess / etiology
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Bevacizumab
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carcinoma / secondary
  • Carcinoma / therapy*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / pathology*
  • Cytoreduction Surgical Procedures / adverse effects*
  • Digestive System Fistula / etiology*
  • Female
  • Fluorouracil / administration & dosage
  • Hematoma / etiology
  • Humans
  • Hyperthermia, Induced*
  • Length of Stay
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Organoplatinum Compounds / administration & dosage
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy*
  • Wound Healing / drug effects

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Bevacizumab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol