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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00797/full |
| _version_ | 1828404807304478720 |
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| author | Raffaele Di Francia Luigi Atripaldi Salvo Di Martino Carla Fierro Tommaso Muto Anna Crispo Sabrina Rossetti Gaetano Facchini Massimiliano Berretta |
| author_facet | Raffaele Di Francia Luigi Atripaldi Salvo Di Martino Carla Fierro Tommaso Muto Anna Crispo Sabrina Rossetti Gaetano Facchini Massimiliano Berretta |
| author_sort | Raffaele Di Francia |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T10:42:12Z |
| format | Article |
| id | doaj.art-c10ebebb3a96435e80258ae72883a647 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T10:42:12Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c10ebebb3a96435e80258ae72883a6472022-12-22T01:52:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-11-01810.3389/fphar.2017.00797286562Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary ResultsRaffaele Di Francia0Luigi Atripaldi1Salvo Di Martino2Carla Fierro3Tommaso Muto4Anna Crispo5Sabrina Rossetti6Gaetano Facchini7Massimiliano Berretta8Hematology-Oncology Unit, Istituto Nazionale Tumori, Fondazione “G. Pascale” IRCCS, Napoli, ItalyHematology and Cellular Immunology (Clinical Biochemistry), A.O. dei Colli Monaldi Hospital, Naples, ItalyCETAC Research Center, Caserta, ItalyHematology and Cellular Immunology (Clinical Biochemistry), A.O. dei Colli Monaldi Hospital, Naples, ItalyHematology and Cellular Immunology (Clinical Biochemistry), A.O. dei Colli Monaldi Hospital, Naples, ItalyEpidemiology-Oncology Unit, Istituto Nazionale Tumori, Fondazione “G. Pascale” IRCCS, Napoli, ItalyMedical Oncology Unit, Istituto Nazionale Tumori, Fondazione “G. Pascale”, Napoli, ItalyMedical Oncology Unit, Istituto Nazionale Tumori, Fondazione “G. Pascale”, Napoli, ItalyDepartment of Medical Oncology, CRO National Cancer Institute, Aviano, ItalyBackbone: 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.http://journal.frontiersin.org/article/10.3389/fphar.2017.00797/fullgenotyping methodsABCB1ABCG2CYP3A4*1BCYP2C8*3ERCC2 |
| spellingShingle | Raffaele Di Francia Luigi Atripaldi Salvo Di Martino Carla Fierro Tommaso Muto Anna Crispo Sabrina Rossetti Gaetano Facchini Massimiliano Berretta Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results Frontiers in Pharmacology genotyping methods ABCB1 ABCG2 CYP3A4*1B CYP2C8*3 ERCC2 |
| 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 | genotyping methods ABCB1 ABCG2 CYP3A4*1B CYP2C8*3 ERCC2 |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00797/full |
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