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MDR1 polymorphism role in patients treated with cetuximab and irinotecan in irinotecan refractory colorectal cancer.
- Source :
-
Medical oncology (Northwood, London, England) [Med Oncol] 2010 Dec; Vol. 27 (4), pp. 1066-72. Date of Electronic Publication: 2009 Oct 28. - Publication Year :
- 2010
-
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.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal, Humanized
Camptothecin administration & dosage
Camptothecin analogs & derivatives
Cetuximab
Colorectal Neoplasms drug therapy
Colorectal Neoplasms pathology
ErbB Receptors metabolism
Female
Humans
Immunoenzyme Techniques
Irinotecan
Liver Neoplasms drug therapy
Liver Neoplasms secondary
Male
Middle Aged
Neoplasm Staging
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins p21(ras)
Survival Rate
Treatment Outcome
ras Proteins genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Colorectal Neoplasms genetics
Drug Resistance, Neoplasm genetics
Liver Neoplasms genetics
Polymorphism, Genetic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1559-131X
- Volume :
- 27
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Medical oncology (Northwood, London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 19862647
- Full Text :
- https://doi.org/10.1007/s12032-009-9336-3