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Severe irinotecan-induced toxicity in a patient with UGT1A1 28 and UGT1A1 6 polymorphisms. | LitMetric

AI Article Synopsis

  • Studies show that UGT1A1 genetic variations, especially UGT1A1 28 (TA 7/7), increase the risk of severe side effects from irinotecan, leading to recommendations for starting at lower doses for affected patients.
  • In Asian populations, the prevalence of UGT1A1 28 (TA 7/7) is lower, while the UGT1A1 6 (A/A) variant, linked to severe neutropenia, is more common.
  • A reported case of a colorectal cancer patient with both UGT1A1 28 (TA 6/7) and UGT1A1 6 (G/A) shows that these combined genetic factors may height

Article Abstract

Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bearing UGT1A1 28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1 28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UGT1A1 28 (TA 7/7), while UGT1A1 6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1 28 polymorphism (TA 6/7) as well as the UGT1A1 6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinotecan dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1 28 and UGT1A1 6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinotecan. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1 28 and UGT1A1 6 polymorphisms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699040PMC
http://dx.doi.org/10.3748/wjg.v19.i24.3899DOI Listing

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