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Medicina (Buenos Aires)

Print version ISSN 0025-7680On-line version ISSN 1669-9106


VALSECCHI, Matías et al. A prevalent genetic variety of UDP-glycuronosyl transferase predicts high risk of irinotecan  toxicity. Medicina (B. Aires) [online]. 2007, vol.67, n.1, pp.57-60. ISSN 0025-7680.

The advances in genetics and molecular biology have raised new areas in  medicine, such as pharmacogenomics, which tries to predict drug responses and toxicities based on the individual genetic variability, describing the so called: pharmacogenomic syndromes. Oncology would find this development extremely useful because of the severe toxicity of chemotherapy. There are a lot of genetic loci under investigation for their potential in predicting drug toxicity, but only three of them have showed clinical usefulness up to now. In particular, quantification of the number of thymine-adenine (TA) dinucleotics in the promoter region of the UDP-glucuronosyl-transferase 1A1 enzime (TA indel) proved to be capable of predicting severe neutropenia in patients exposed to intermediate or high doses of irinotecan. Herein we report a case of a patient with small cell lung cancer who suffered severe hematological and gastrointestinal toxicity after being treated with relatively low doses (65 mg/m2) of irinotecan and whose leucocyte DNA analysis showed the presence of seven TA repetitions in both alleles. This case is an example of the clinical applicability and the utility of the test as a toxicity predictor. We also discuss the clinical decisions that may be taken with these patients.

Keywords : Irinotecan; Pharmacogenomics; UGT 1A1; TA indel.

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