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Absence of effect of SLC 22A2 genotype on cisplatin‐induced nephrotoxicity in oesophageal cancer patients receiving cisplatin and 5‐fluorouracil: report of results discordant with those of earlier studies
Author(s) -
Hinai Y.,
Motoyama S.,
Niioka T.,
Miura M.
Publication year - 2013
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12097
Subject(s) - nephrotoxicity , cisplatin , chemotherapy , medicine , regimen , genotyping , renal function , oncology , chemotherapy regimen , genotype , fluorouracil , gastroenterology , urology , kidney , biology , biochemistry , gene
Summary What is known and objective Cancer patients treated with cisplatin chemotherapy frequently experience drug‐induced nephrotoxicity. Clinical studies using a single chemotherapeutic regimen or large sample sizes for patients with the SLC 22A2 808T allele have not been reported. Here, we examined 95 patients with oesophageal cancer who received 5‐fluorouracil and cisplatin ( FP ) to determine whether nephrotoxicity was affected by SLC 22A2 808G>T polymorphism. Methods The change rate of the estimated glomerular filtration rate (e GFR ) was used for the evaluation of cisplatin‐induced nephrotoxicity and calculated for each patient according to the following formula: change rate = (prechemotherapy value – post‐chemotherapy value)/prechemotherapy value. Genotyping of SLC22A2 808G>T was carried out using the polymerase chain reaction–restriction fragment length polymorphism ( PCR ‐ RFLP ) method. Results The e GFR after FP chemotherapy was significantly lower than that before chemotherapy, and the mean difference in e GFR was 25·7 mL/min ( P < 0·01). There was no significant difference in the mean change rate of the e GFR following FP chemotherapy between the SLC22A2 808GG genotype ( n = 70) and the 808GT+TT genotypes ( n = 25) (27·9% and 27·8%, respectively). In multiple regression analyses, the change rate of e GFR following FP chemotherapy was associated with the e GFR value prior to chemotherapy ( P = 0·04). What is new and conclusion In FP chemotherapy for oesophageal cancers, cisplatin‐induced nephrotoxicity seems to be unaffected by the SLC22A2 808G>T polymorphism. The e GFR prior to chemotherapy might be an important risk factor for cisplatin‐induced nephrotoxicity. Our present study was estimated with a single chemotherapeutic regimen, e GFR , and was calculated using serum creatinine, age and the sex of the patient and sample sizes of 25 patients with SLC22A2 808T allele. However, further examinations with a larger sample size to corroborate the study results might be necessary.