UGT1A128 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study

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 ⩾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. 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.