Garcia Andrew, Frahm Corey, Jeter Joanne M, Abraham Ivo, Chambers Setsuko K, Cragun Janiel M, McBride Ali
University of Arizona College of Pharmacy, Tucson, Arizona.
Divisions of Human Genetics and Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
J Adv Pract Oncol. 2019 Jul;10(5):428-439. doi: 10.6004/jadpro.2019.10.5.2. Epub 2019 Jul 1.
The association of mutation status with hypersensitivity reactions (HSRs) to carboplatin has gained interest in recent years, particularly in patients with ovarian, fallopian tube, and primary peritoneal cancer. The primary objective of this study is to determine whether the presence of mutations increased the likelihood of HSRs to carboplatin. The incidence of HSRs to paclitaxel and symptom grade based on the Common Terminology Criteria for Adverse Events, version 4.0, were explored as secondary endpoints. A retrospective chart review of patients with ovarian, fallopian tube, or primary peritoneal cancer at the University of Arizona Cancer Center who underwent treatment with carboplatin-containing regimens and received genetic testing was performed. Institutional review board approval was obtained for this study. Fisher's exact test was used to analyze the primary outcome. Out of 167 initial patients, 62 with germline test results constituted the evaluable sample. 15 of 62 (24.2%) -tested patients were treated with carboplatin monotherapy, while 44 of 62 (71.0%) patients were treated with paclitaxel-containing regimens. Hypersensitivity reactions occurred in 4 of 13 (30.8%) -mutated patients and 22 of 49 (44.9%) wild-type patients ( = .5291). Hypersensitivity reactions to paclitaxel occurred in 1 of 13 (7.7%) -mutated patients and 26 of 49 (53.1%) wild-type patients ( = .0039). Overall, there were 11 grade 1 reactions, 14 grade 2 reactions, and 16 grade 3 reactions to carboplatin. All reactions to carboplatin in -mutated patients were grade 1. All paclitaxel reactions manifested as grade 2. The sample size was the main study limitation. The presence of mutations was not statistically significantly associated with a higher incidence of HSRs to carboplatin, but was statistically significant with regards to paclitaxel.
近年来，突变状态与对卡铂的超敏反应（HSR）之间的关联受到了关注，尤其是在卵巢癌、输卵管癌和原发性腹膜癌患者中。本研究的主要目的是确定突变的存在是否会增加对卡铂发生HSR的可能性。作为次要终点，探讨了根据《不良事件通用术语标准》第4.0版对紫杉醇发生HSR的发生率和症状分级。对亚利桑那大学癌症中心接受含卡铂方案治疗并接受基因检测的卵巢癌、输卵管癌或原发性腹膜癌患者进行了回顾性病历审查。本研究获得了机构审查委员会的批准。采用Fisher精确检验分析主要结果。在167例初始患者中，62例有生殖系检测结果的患者构成了可评估样本。62例接受检测的患者中有15例（24.2%）接受了卡铂单药治疗，而62例患者中有44例（71.0%）接受了含紫杉醇的方案治疗。13例突变患者中有4例（30.8%）发生超敏反应，49例野生型患者中有22例（44.9%）发生超敏反应（P = 0.5291）。13例突变患者中有1例（7.7%）对紫杉醇发生超敏反应，49例野生型患者中有26例（53.1%）发生超敏反应（P = 0.0039）。总体而言，对卡铂有11例1级反应、14例2级反应和16例3级反应。突变患者对卡铂的所有反应均为1级。所有紫杉醇反应均表现为2级。样本量是主要的研究局限性。突变的存在与对卡铂发生HSR的较高发生率在统计学上无显著关联，但与紫杉醇有关在统计学上有显著意义。
