Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results.
Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results.
复制标题
DOI：
10.3389/fphar.2017.00797
复制
发表时间：
2017
影响因子：
5.6
通讯作者：
Berretta M
中科院分区：
文献类型：
--
作者：
Di Francia R;Atripaldi L;Di Martino S;Fierro C;Muto T;Crispo A;Rossetti S;Facchini G;Berretta M
骨干：紫杉醇和多西他赛是主要的紫杉烷类抗癌药物，常用于治疗乳腺、胃、卵巢、头/颈、肺和泌尿生殖系统肿瘤。暂停紫杉烷治疗损害患者的利益，更经常引起周围神经病变和过敏，而不是肿瘤进展。到目前为止，已经研究了几种预防毒性的策略。最近，研究结果的遗传变异与毒性和耐药性的紫杉烷为基础的化疗已被报道。研究方法：一个广泛的面板上的四个候选基因（ABCB 1，CYP 2C 8 *3，CYP 3A 4 *1B，XRCC 3），以前验证为与紫杉醇和多西他赛毒性的显着标志物的五个多态性进行了分析和讨论。我们对76名癌症患者进行了基因分型，其中35人接受了紫杉醇或紫杉醇为基础的治疗。此外，对基因分型的成本和效益进行了早期概要评估。结果：在35例接受紫杉烷类药物治疗的患者中，6例（17.1%）发生了不良神经病变事件。药物基因组学分析显示，候选基因多态性与毒性之间无相关性，但XRCC 3 AG+GG等位基因[OR 2.61（95% CI：0.91-7.61）]与AG等位基因[OR 1.52（95% CI：0.51-4.91）]相比，显示神经毒性风险的显著性趋势较弱，P = 0.03。总结：根据我们的实验结果和文献数据，我们提出了一种有用的和低成本的基因分型面板检测，用于预防接受紫杉烷为基础的治疗的患者的毒性。有了个体药物基因组学特征，临床医生将有更多的信息来为他们的患者计划更好的治疗，以最大限度地减少毒性和最大限度地提高效益，包括确定国家医疗保健可持续性的成本效益。
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.
登录
查看更多内容
影响因子：
5.7
作者：
Kim HJ;Im SA;Keam B;Ham HS;Lee KH;Kim TY;Kim YJ;Oh DY;Kim JH;Han W;Jang IJ;Kim TY;Park IA;Noh DY
通讯作者：
Noh DY
DOI：
10.1158/1078-0432.ccr-12-3786
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
de Graan AJ;Elens L;Sprowl JA;Sparreboom A;Friberg LE;van der Holt B;de Raaf PJ;de Bruijn P;Engels FK;Eskens FA;Wiemer EA;Verweij J;Mathijssen RH;van Schaik RH
通讯作者：
van Schaik RH
XRCC3 Thr241Met 与晚期非小细胞肺癌对铂类化疗的反应相关，但与生存无关。
影响因子：
3.7
作者：
Qiu M;Xu L;Yang X;Ding X;Hu J;Jiang F;Xu L;Yin R
通讯作者：
Yin R
影响因子：
2.8
作者：
Bergmann, T. K.;Brasch-Andersen, C.;Brosen, K.
通讯作者：
Brosen, K.
DOI：
10.1111/j.1742-7843.2008.00351.x
发表时间：
2009-02-01
影响因子：
3.1
作者：
Green, Henrik;Soderkvist, Peter;Peterson, Curt
通讯作者：
Peterson, Curt