Clinical-pharmacogenetic models for personalized cancer treatment: application to malignant mesothelioma.

ABSTRACT: Large interindividual differences in treatment outcome are observed in cancer patients undergoing chemotherapy. Our aim was to develop and validate clinical-pharmacogenetic prediction models of gemcitabine/cisplatin or pemetrexed/cisplatin treatment outcome and develop an algorithm for genotype-based treatment recommendations in malignant mesothelioma (MM). We genotyped 189?MM patients for polymorphisms in gemcitabine, pemetrexed and cisplatin metabolism, transport and drug target genes and DNA repair pathways. To build respective clinical-pharmacogenetic models, pharmacogenetic scores were assigned by rounding regression coefficients. Gemcitabine/cisplatin model was based on training group of 71 patients and included CRP, histological type, performance status, RRM1 rs1042927, ERCC2 rs13181, ERCC1 rs3212986, and XRCC1 rs25487. Patients with higher score had shorter progression-free (PFS) and overall survival (P?

SUBMITTER: Goricar K 

PROVIDER: S-EPMC5396189 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature