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Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results
Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, tha...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682021/ https://www.ncbi.nlm.nih.gov/pubmed/29163177 http://dx.doi.org/10.3389/fphar.2017.00797 |
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author | Di Francia, Raffaele Atripaldi, Luigi Di Martino, Salvo Fierro, Carla Muto, Tommaso Crispo, Anna Rossetti, Sabrina Facchini, Gaetano Berretta, Massimiliano |
author_facet | Di Francia, Raffaele Atripaldi, Luigi Di Martino, Salvo Fierro, Carla Muto, Tommaso Crispo, Anna Rossetti, Sabrina Facchini, Gaetano Berretta, Massimiliano |
author_sort | Di Francia, Raffaele |
collection | PubMed |
description | Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported. Methods: An extensive panel of five polymorphisms on four candidate genes (ABCB1, CYP2C8(*)3, CYP3A4(*)1B, XRCC3), previously validated as significant markers related to paclitaxel and Docetaxel toxicity, are analyzed and discussed. We genotyped 76 cancer patients, and 35 of them received paclitaxel or docetaxel-based therapy. What is more, an early outline evaluation of the genotyping costs and benefit was assessed. Results: Out of 35 patients treated with a taxane, six (17.1%) had adverse neuropathy events. Pharmacogenomics analysis showed no correlation between candidate gene polymorphisms and toxicity, except for the XRCC3 AG+GG allele [OR 2.61 (95% CI: 0.91–7.61)] which showed a weak significant trend of risk of neurotoxicities vs. the AG allele [OR 1.52 (95% CI: 0.51–4.91)] P = 0.03. Summary: Based on our experimental results and data from the literature, we propose a useful and low-cost genotyping panel assay for the prevention of toxicity in patients undergoing taxane-based therapy. With the individual pharmacogenomics profile, clinicians will have additional information to plan the better treatment for their patients to minimize toxicity and maximize benefits, including determining cost-effectiveness for national healthcare sustainability. |
format | Online Article Text |
id | pubmed-5682021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56820212017-11-21 Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results Di Francia, Raffaele Atripaldi, Luigi Di Martino, Salvo Fierro, Carla Muto, Tommaso Crispo, Anna Rossetti, Sabrina Facchini, Gaetano Berretta, Massimiliano Front Pharmacol Pharmacology Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported. Methods: An extensive panel of five polymorphisms on four candidate genes (ABCB1, CYP2C8(*)3, CYP3A4(*)1B, XRCC3), previously validated as significant markers related to paclitaxel and Docetaxel toxicity, are analyzed and discussed. We genotyped 76 cancer patients, and 35 of them received paclitaxel or docetaxel-based therapy. What is more, an early outline evaluation of the genotyping costs and benefit was assessed. Results: Out of 35 patients treated with a taxane, six (17.1%) had adverse neuropathy events. Pharmacogenomics analysis showed no correlation between candidate gene polymorphisms and toxicity, except for the XRCC3 AG+GG allele [OR 2.61 (95% CI: 0.91–7.61)] which showed a weak significant trend of risk of neurotoxicities vs. the AG allele [OR 1.52 (95% CI: 0.51–4.91)] P = 0.03. Summary: Based on our experimental results and data from the literature, we propose a useful and low-cost genotyping panel assay for the prevention of toxicity in patients undergoing taxane-based therapy. With the individual pharmacogenomics profile, clinicians will have additional information to plan the better treatment for their patients to minimize toxicity and maximize benefits, including determining cost-effectiveness for national healthcare sustainability. Frontiers Media S.A. 2017-11-07 /pmc/articles/PMC5682021/ /pubmed/29163177 http://dx.doi.org/10.3389/fphar.2017.00797 Text en Copyright © 2017 Di Francia, Atripaldi, Di Martino, Fierro, Muto, Crispo, Rossetti, Facchini and Berretta. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Di Francia, Raffaele Atripaldi, Luigi Di Martino, Salvo Fierro, Carla Muto, Tommaso Crispo, Anna Rossetti, Sabrina Facchini, Gaetano Berretta, Massimiliano Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results |
title | Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results |
title_full | Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results |
title_fullStr | Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results |
title_full_unstemmed | Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results |
title_short | Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results |
title_sort | assessment of pharmacogenomic panel assay for prediction of taxane toxicities: preliminary results |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682021/ https://www.ncbi.nlm.nih.gov/pubmed/29163177 http://dx.doi.org/10.3389/fphar.2017.00797 |
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