(see blog for comments) UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Sunday, November 27, 2016

(see blog for comments) UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan



 Blogger's Note (comments-mine): 1) Japan has a much higher rate of clear cell ovarian cancer than Western countries and, as well, presents more often in early stages; 2) trials on CPT-11 (Irinotecan) started a couple of decades ago and seemed in the Japanese trial patients to confer a survival advantage; 3) published longterm data results (2016) were negative; 4) full text of this article is subscriber-based but this abstract may be a sub-analysis (hard to tell from abstract) and references are not attached to the abstract
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UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan

 We investigated whether UGT1A1 polymorphisms are associated with the prognosis of ovarian cancer patients treated with irinotecan. UGT1A1 genotypes were analyzed in 11 stage I ovarian clear cell carcinoma patients who received irinotecan as first-line therapy. Progression-free survival, overall survival and adverse events were also assessed for each genotype. Three patients harbored UGT1A1*1/*6 while another three harbored UGT1A1*1/*28. Two patients with a wild-type genotype experienced recurrence and one died, whereas no recurrence or death was observed in patients with heterozygous genotypes. Adverse events tended to be more severe in patients with UGT1A1*6 and *28, although progression-free survival and overall survival rates tended to be better than in wild-type; the differences were not significant. We conclude that UGT1A1 polymorphisms have the potential to be a prognostic marker of irinotecan treatment.
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Wiki:
Pharmacogenetics
Genetic variations within the UGT1A1 gene have also been associated with the development of certain drug toxicities. The UGT1A1*28 variant, the same allele behind many cases of Gilbert syndrome, has been associated with an increased risk for neutropenia in patients receiving the chemotherapeutic drug irinotecan,[15][16] and the U.S. Food and Drug Administration recommends on the irinotecan drug label that patients with the *28/*28 genotype receive a lower starting dose of the drug.[17] The *28 allele has also shown associations with an increased risk for developing diarrhea in patients receiving irinotecan.[15][16] The UGT1A1*6 variant, more common in Asian populations than the *28 variant, has also shown associations with the development of irinotecan toxicities. Patients who are heterozygous or homozygous for the *6 allele may have a higher risk for developing neutropenia and diarrhea as compared to those with the UGT1A1*1/*1 genotype.[15][16]

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