Medical Oncology

, Volume 27, Issue 4, pp 1066–1072

MDR1 polymorphism role in patients treated with cetuximab and irinotecan in irinotecan refractory colorectal cancer

  • Bernard Paule
  • Vincent Castagne
  • Véronique Picard
  • Raphaël Saffroy
  • René Adam
  • Catherine Guettier
  • Robert Farinotti
  • Laurence Bonhomme-Faivre
Original Paper

DOI: 10.1007/s12032-009-9336-3

Cite this article as:
Paule, B., Castagne, V., Picard, V. et al. Med Oncol (2010) 27: 1066. doi:10.1007/s12032-009-9336-3

Abstract

The aim of the study was to evaluate the influence of the MDR1 C3435T polymorphism on the therapeutic response in 23 patients treated with cetuximab plus irinotecan for irinotecan refractory liver metastatic colorectal cancer considering their KRAS status. Indeed, irinotecan and its active metabolite (SN-38) are both substrates of P-glycoprotein (P-gp) encoded by MDR1. Patients received cetuximab and irinotecan up to progression. The overall survival was 55% at 10 months. Overall, four patients had an undetermined KRAS status and two patients with mutated KRAS were in progression disease. The response to treatment was observed after 3 months among the 17 wild-type KRAS patients. Two patients presented a progressive disease (1 TT and 1 CT), eight patients had a stable disease (5 CC and 3CT) and five patients had a partial response (3 CC and 2 CT). Importantly, 2 patients (2 TT) were in complete response and still alive 5 years after starting the treatment, which suggests that the combination of wild-type KRAS and MDR1 3435 TT may be a factor of good prognosis. These results suggest that EGFR inhibition by cetuximab may overcome this irinotecan resistance by abrogating drug efflux depending on MDR1 3435 polymorphism. Among patients resistant to irinotecan, it is still possible to use the association of cetuximab plus irinotecan to obtain a complete resection of hepatic metastases that is necessary to improve their survival.

Keywords

KRAS mutationCetuximabIrinotecanP-glycoproteinMDR1 polymorphismEGFRColorectal cancer

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Bernard Paule
    • 1
  • Vincent Castagne
    • 2
  • Véronique Picard
    • 4
  • Raphaël Saffroy
    • 5
  • René Adam
    • 1
  • Catherine Guettier
    • 3
  • Robert Farinotti
    • 4
  • Laurence Bonhomme-Faivre
    • 2
    • 4
  1. 1.Centre Hépatobiliaire, Paul Brousse University HospitalVillejuifFrance
  2. 2.Department of Pharmacy-PharmacologyPaul Brousse University HospitalVillejuifFrance
  3. 3.Department of PathologyPaul Brousse University HospitalVillejuifFrance
  4. 4.UPRES 2706 Barrière et Passage des médicamentsUniversité Paris Sud 11, Faculté de PharmacieParis XIFrance
  5. 5.Department of Biochemistry, INSERM U602Paul Brousse University HospitalVillejuifFrance