Impact of Cytidine Deaminase Polymorphisms on Toxicity After Gemcitabine: The Question Is

TO THE EDITOR:We have read with interest the article by Cicco-lini et al1 reporting data from an observational study where they retrospectivelyexaminedadverseevents fromthreecohortsofpatients treated with gemcitabine, alone or combined with other drugs, and evaluated the activity of cytidine deaminase (CDA) in serum. For that purpose, theyuseda test thatwasvalidated inamousemodel, showing that CDAdeficiency increased gemcitabine plasma levels, with subse-quent lethal toxicities. In addition, they performed genotyping analy-ses for three polymorphisms of theCDA gene. They demonstrated that patients with toxicities had a signifi-cantly lower CDA activity than patients without toxicities, even as no genotype-phenotype relationships were found, and concluded that determination of CDA activity is the most reliable test to identify patients at risk of developing severe toxicities with gemcitabine. The critical role of CDA in gemcitabine activity/toxicity has bee