Mysona David, Dorr Katherine, Ward Alex, Shaver Ellen, Rungruang Bunja, Ghamande Sharad
The Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA; Center for Biotechnology and Genomic Medicine at Augusta University, Augusta, GA 30912, USA.
The Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA.
Gynecol Oncol. 2023 Jan;168:114-118. doi: 10.1016/j.ygyno.2022.10.021. Epub 2022 Nov 23.
This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy.
Patients were enrolled from August 2020 to November 2020 in a prospective, case-control trial evaluating pharmacogenetic predictors of CIPN. All women were treated with at least 3 cycles of taxane-based chemotherapy for histologically confirmed gynecologic malignancies. Buccal saliva samples were used to test for 32 drug metabolism variations. All testing was performed by ⍺LPHA-GENOMIX laboratories. Fisher's Exact test was used to assess for event differences of categorical variables.
Of 102 enrolled patients, 58%, 28%, and 14% had ovarian, endometrial, or cervical cancers, respectively. The median age was 67, 72% were Caucasian and 25% were African American. 16% of patients were treated with 3-4 cycles, 57% received 5-7 cycles, and 27% received 8 or more cycles of chemotherapy that included paclitaxel. Grade 2 CIPN was experienced by 51 patients. There was no difference in age, race, disease site, or number of chemotherapy cycles (p > 0.05) between those who did or did not develop CIPN. CYP2D6 genotype (p = 0.009) and CYP3A5 genotype (p = 0.023) had different frequencies among those with and without CIPN. Patients classified as having poor or intermediate function of CYP2D6 had increased risk of CIPN (OR 1.63, 95% CI 1.04-2.57, p = 0.026). There was no difference in CYP2D6 phenotype by race (p = 0.29). No patients with normal function of CYP3A5 developed CIPN. There were no Caucasians with normal function of CYP3A5, but 28% of African Americans had normal CYP3A5 function (p < 0.001).
Pharmacogenomics appear associated with the development of CIPN and may be able to help personalize treatment decision making.
本研究调查了是否存在可预测基于紫杉烷的化疗所致化疗引起的周围神经病变（CIPN）的药物基因组学标志物。
2020年8月至2020年11月，患者被纳入一项前瞻性病例对照试验，评估CIPN的药物遗传学预测指标。所有女性均接受至少3个周期的基于紫杉烷的化疗，用于组织学确诊的妇科恶性肿瘤。使用颊部唾液样本检测32种药物代谢变异。所有检测均由⍺LPHA-GENOMIX实验室进行。采用Fisher精确检验评估分类变量的事件差异。
102名入组患者中，分别有58%、28%和14%患有卵巢癌、子宫内膜癌或宫颈癌。中位年龄为67岁，72%为白种人，25%为非裔美国人。16%的患者接受了3 - 4个周期的治疗，57%接受了5 - 7个周期的治疗，27%接受了包括紫杉醇在内的8个或更多周期的化疗。51名患者出现2级CIPN。发生或未发生CIPN的患者在年龄、种族、疾病部位或化疗周期数方面无差异（p>0.05）。CYP2D6基因型（p = 0.009）和CYP3A5基因型（p = 0.023）在发生和未发生CIPN的患者中频率不同。被分类为CYP2D6功能差或中等的患者发生CIPN的风险增加（OR 1.63，95% CI 1.04 - 2.57，p = 0.026）。种族间CYP2D6表型无差异（p = 0.29）。CYP3A5功能正常的患者均未发生CIPN。没有白种人的CYP3A5功能正常，但28%的非裔美国人CYP3A5功能正常（p<0.001）。
药物基因组学似乎与CIPN的发生有关，可能有助于个性化治疗决策。
