UGT1A1*28 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.