1. ¹Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, The Netherlands
2. ²Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, The Netherlands
3. ³Biometrics Department, Netherlands Cancer Institute (NKI), Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands
4. ⁴Department of Oncology, Radboud University Nijmegen Medical Center, Geert Grooteplein-Zuid 10, Nijmegen 6525 GA, The Netherlands

Correspondence: DM Kweekel, Leiden University Medical Center (LUMC), Department of Clinical Pharmacy and Toxicology (L-0-P), 2300 RC Leiden, The Netherlands. E-mail d.m.kweekel@lumc.nl

Revised 9 May 2008; Accepted 12 May 2008; Published online 1 July 2008.

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. TA₇ homozygotes receiving irinotecan combination therapy had a higher incidence of febrile neutropenia (18.2%) compared to the other genotypes (TA₆/TA₆ : 1.5%; TA₆/TA₇ : 6.5%, P=0.031). TA₇ heterozygotes receiving irinotecan monotherapy also suffered more febrile neutropenia (19.4%) compared to TA₆/TA₆ 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. TA₇ homozygotes did not receive a lower median irinotecan dose, number of cycles (P-values 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 3 diarrhoea, not (febrile) neutropenia. TA₇/TA₇ 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.