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Case Reports
. 2013 Jun 28;19(24):3899-903.
doi: 10.3748/wjg.v19.i24.3899.

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

Jian-Ming Xu  1 , Yan Wang, Fei-Jiao Ge, Li Lin, Ze-Yuan Liu, Manish R Sharma
Affiliations
Case Reports

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

Jian-Ming Xu et al. World J Gastroenterol. .

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.

Keywords: Irinotecan; Polymorphism; Toxicity; UGT1A1*28; UGT1A1*6.

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Figures

Figure 1
Figure 1
Plasma concentration-time profiles of SN-38 in different dose levels of irinotecan.
Figure 2
Figure 2
Computerized tomography scan (A) and magnetic resonance imaging (B). Before treatment (left figure) and after treatment (right figure) of the lung and the liver metastases, respectively; the response was confirmed after two additional cycles.
See this image and copyright information in PMC

References

    1. Palomaki GE, Bradley LA, Douglas MP, Kolor K, Dotson WD. Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review. Genet Med. 2009;11:21–34. - PMC - PubMed
    1. Wang Y, Shen L, Xu N, Wang JW, Jiao SC, Liu ZY, Xu JM. UGT1A1 predicts outcome in colorectal cancer treated with irinotecan and fluorouracil. World J Gastroenterol. 2012;18:6635–6644. - PMC - PubMed
    1. Di Paolo A, Bocci G, Polillo M, Del Re M, Di Desidero T, Lastella M, Danesi R. Pharmacokinetic and pharmacogenetic predictive markers of irinotecan activity and toxicity. Curr Drug Metab. 2011;12:932–943. - PubMed
    1. Cecchin E, Innocenti F, D’Andrea M, Corona G, De Mattia E, Biason P, Buonadonna A, Toffoli G. Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan. J Clin Oncol. 2009;27:2457–2465. - PubMed
    1. Strassburg CP, Kalthoff S, Ehmer U. Variability and function of family 1 uridine-5’-diphosphate glucuronosyltransferases (UGT1A) Crit Rev Clin Lab Sci. 2008;45:485–530. - PubMed

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