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Single nucleotide polymorphisms to predict taxanes toxicities and effectiveness in cancer patients

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Abstract

Taxanes are used in the treatment of several solid tumours. Adverse events (AEs) might be influenced by single nucleotide polymorphisms (SNPs) in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. In this prospective, monocentric, observational study we explored the effect of SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy in 125 patients (pts) treated with paclitaxel, nab-paclitaxel, or docetaxel for neoplasms. There was no statistically significant association between the investigated SNPs and AEs. The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). CYP2C8*3/*4 variant carriers showed a trend of association with overall AEs in pts treated with paclitaxel and nab-paclitaxel (RR = 1.28; 95% CI 0.96, 1.67; p = 0.0898). No statistically significant relationship with treatment efficacy was found. ABCB1 3435TT showed a trend of association with a higher treatment response (RR = 0.22; 95% CI 0.03, 1.51; p = 0.0876). Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found.

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Authors and Affiliations

  1. Department of Oncology, Luigi Sacco University Hospital, ASST Fatebenefratelli—Sacco, Milan, Italy

    Sara Demurtas, Nicla La Verde, Selene Rota, Maria Silvia Cona, Davide Dalu, Cinzia Fasola, Sabrina Ferrario, Virginio Filipazzi, Anna Gambaro & Nicoletta Tosca

  2. Department of Biomedical and Clinical Sciences “L. Sacco”, Università degli Studi di Milano, Milan, Italy

    Giovanni Casazza & Emilio Clementi

  3. Unit of Clinical Pharmacology, Luigi Sacco University Hospital, ASST Fatebenefratelli—Sacco, Milan, Italy

    Cristina Montrasio, Stefania Cheli & Emilio Clementi

  4. Eugenio Medea Scientific Institute, Bosisio Parini, Italy

    Emilio Clementi

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  1. Sara Demurtas
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Correspondence to Davide Dalu.

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LVN reports: grants from Eisai; speaker bureau, travel expenses for conference from Roche and Gentili; advisory role from Novartis and Celgene; advisor role, travel expenses for conference from Pfizer; advisory board from MSD. The other authors declare that they have no conflict of interest.

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Demurtas, S., La Verde, N., Rota, S. et al. Single nucleotide polymorphisms to predict taxanes toxicities and effectiveness in cancer patients. Pharmacogenomics J 21, 491–497 (2021). https://doi.org/10.1038/s41397-021-00227-7

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