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- Title
UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study.
- Authors
Kweekel, D M; Gelderblom, H; Van der Straaten, T; Antonini, N F; Punt, C J A; Guchelaar, H-J; Dutch Colorectal Cancer Group study
- Abstract
The aim of the study was to investigate the associations between UGT1A1(*)28 genotype and (1) response rates, (2) febrile neutropenia and (3) dose intensity in patients with metastatic colorectal cancer treated with irinotecan. UGT1A1(*)28 genotype was determined in 218 patients receiving irinotecan (either first-line therapy with capecitabine or second-line as monotherapy) for metastatic colorectal cancer. TA(7) homozygotes receiving irinotecan combination therapy had a higher incidence of febrile neutropenia (18.2%) compared to the other genotypes (TA(6)/TA(6) : 1.5%; TA(6)/TA(7) : 6.5%, P=0.031). TA(7) heterozygotes receiving irinotecan monotherapy also suffered more febrile neutropenia (19.4%) compared to TA(6)/TA(6) genotype (2.2%; P=0.015). Response rates among genotypes were not different for both regimens: combination regimen, P=0.537; single-agent, P=0.595. TA(7) homozygotes did not receive a lower median irinotecan dose, number of cycles (P-values >or=0.25) or more frequent dose reductions compared to the other genotypes (P-values for trend; combination therapy: 0.62 and single-agent: 0.45). Reductions were mainly (>80%) owing to grade >or=3 diarrhoea, not (febrile) neutropenia. TA(7)/TA(7) patients have a higher incidence of febrile neutropenia upon irinotecan treatment, but were able to receive similar dose and number of cycles compared to other genotypes. Response rates were not significantly different.
- Subjects
FEBRILE neutropenia; NEUTROPENIA; CANCER patients; GENETIC polymorphisms; THERAPEUTICS; GENETIC research; COLON cancer; PATIENTS
- Publication
British Journal of Cancer, 2008, Vol 99, Issue 2, p275
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/sj.bjc.6604461