The value of genetic polymorphisms to predict toxicity in metastatic colorectal patients with irinotecan-based regimens
Cancer Chemotherapy and Pharmacology, 05/01/2012
Lamas MJ et al. – The impact of increased risk of toxicity attributed to the UGT1A variants may be offset by irinotecan in clinical practice by dose reduction or the use of colony–stimulating factor.
Genomic DNA was genotyped for UGT1A1 (*28, *60 and *93) from all 101 patients, and irinotecan dose was 180mg/m
2 every second week. Clinical data were obtained by retrospective chart review.
The primary endpoint is to find out whether the pharmacogenetic test in the clinical practice may predict toxicity.
Grade 3/4 diarrhea occurred in twelve patients and required dose reduction in six patients, and neutropenia reached grade 3/4 in 19 patients (only one patient with *28/*28 genotype).
The UGT1A1*93 seemed to relate with grade 3/4 neutropenia but only in the heterozygote state (G/A), p=0.071, and UGT1A*60 showed no association with neutropenia.
Twenty-eight percentage of patients required the use of G-CSF; 64.3 % of them harbored *1/*28 or *28/*28 genotypes, p=0.003.
Thirty-seven (36.6 %) patients required dose reduction of irinotecan and/or 5-FU owing to toxicity, mainly neutropenia and diarrhea.
No significant association was detected between *28, *60 and *93 UGT1A variants and severe irinotecan-associated hematologic or GI toxicity.