Abstract
Background: Chemotherapy-induced nausea and vomiting (CINV) are one of the most unpleasant non-haematological adverse effects that affect the well-being of cancer patients. The aim of this study was to evaluate the association between the antiemetic efficacy and the ABC genetic polymorphisms and clarify the risk of CINV.Methods: Patients receiving highly emetogenic chemotherapy were examined for antiemetic responses to aprepitant in combination with granisetron and dexamethasone. The efficacy endpoint of this study was complete response (no vomiting and no use of rescue medications). Patient DNA samples were genotyped for ABCB1 and ABCG2 single nucleotide polymorphism. In this study, the impact on complete response of treatment and a number of prespecified risk factors, including gender, age, performance status (PS) and alcohol use was assessed. Complete response and the associations with patients factor including genetic polymorphisms were evaluated in acute and in delayed phases using univariate and multivariate analyses.Results: Sixty-eight patients receiving doxorubicin plus cyclophosphamide chemotherapy and 30 patients receiving cisplatin containing chemotherapy were evaluated. The multivariate logistic regression analyses showed that female gender (odds ratio [OR], 7.17; 95% confidence interval [CI] 1.43-35.82), age <50 years (OR 4.02; 95%CI 1.42-11.36), ABCB1 1236 TT (OR 3.27; 95%CI 1.18-9.07), and ABCG2 421 AA (OR 0.09; 95%CI 0.01-0.93) were associated with antiemetic treatment failure in the acute phase. In contrast, only female gender (OR 14.30; 95%CI 4.38-46.71) was associated in the delayed phase.Conclusions: In addition to gender and age known to be risk factors for CINV, ABC transporter polymorphisms may influence the extent of acute CINV control in aprepitant, granisetron and dexamethasone-treated patients. ABC genotypes might be a predictor of antiemetic response in acute phase.
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