Cetuximab plus irinotecan in heavily pretreated metastatic colorectal cancer progressing on irinotecan: MABEL Study

J Clin Oncol. 2008 Nov 20;26(33):5335-43. doi: 10.1200/JCO.2008.16.3758. Epub 2008 Oct 14.

Abstract

Purpose: This large, multinational study aimed to confirm in a community practice setting the efficacy and safety of cetuximab plus irinotecan in patients with epidermal growth factor-expressing metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen.

Patients and methods: The primary objective was to determine the progression-free survival (PFS) rate at 12 weeks. The initial cetuximab dose was 400 mg/m(2) and was followed weekly by 250 mg/m(2); irinotecan (according to prestudy regimen) was given weekly (125 mg/m(2) weekly for 4 of 6 weeks), every 2 weeks (180 mg/m(2) each), or every 3 weeks (350 mg/m(2) each).

Results: The intention-to-treat/safety population comprised 1,147 treated patients who received irinotecan weekly (n = 93); every 2 weeks (n = 670); every 3 weeks (n = 356); or another dose (n = 28). The PFS rate at 12 weeks was 61%, and the median survival was 9.2 months. Treatment was generally well tolerated. The most common treatment-related grades 3 to 4 adverse events were diarrhea (19%), neutropenia (10%), rash (7%), and asthenia (6%). The rate of grades 3 to 4 infusion-related reactions (IRRs; composite adverse event category) was 1% for patients who received both antihistamine and corticosteroid premedication. CONCLUSION Tolerability (except IRR incidence), PFS rate, and overall survival rate were in line with previous results. At 1%, the rate of IRRs in patients who received prophylactic premedication with both antihistamine and corticosteroid is lower than previously reported. MABEL clearly confirms in a community practice setting the efficacy and safety of cetuximab plus irinotecan in the treatment of mCRC.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Cetuximab
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Female
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Irinotecan
  • Cetuximab
  • Camptothecin