The value of genetic polymorphisms to predict toxicity in metastatic colorectal patients with irinotecan-based regimens
Cancer Chemotherapy and Pharmacology,  Clinical Article

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.

Methods
  • Genomic DNA was genotyped for UGT1A1 (*28, *60 and *93) from all 101 patients, and irinotecan dose was 180mg/m2 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.

Results
  • 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.

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