Matsui Reiko, Suzuki Kenichi, Takiguchi Tomomi, Nishio Makoto, Koike Takeshi, Hayashi Toshinobu, Seto Takashi, Kogure Yuki, Nogami Naoyuki, Fujiwara Kimiko, Kaneda Hiroyasu, Harada Tomohiko, Shimizu Satoru, Kimura Masashi, Kenmotsu Hirotsugu, Shimokawa Mototsugu, Goto Koichi
Department of Pharmacy, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.
Department of Pharmacy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan.
BMC Pharmacol Toxicol. 2020 Oct 6;21(1):72. doi: 10.1186/s40360-020-00445-y.
Of patients receiving moderate emetic risk chemotherapy (MEC), 30-90% experience chemotherapy-induced nausea and vomiting (CINV); however, the optimal antiemetic treatment remains controversial.
In this multicenter, prospective, observational study of adults treated with MEC while receiving chemotherapy for various cancer types in Japan, the enrolled patients kept diaries documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone.
Of the 400 patients enrolled from May 2013 to January 2015, 386 were eligible for evaluation. The median age was 64 (range, 26-84). The overall complete response (CR; no emetic events and no antiemetic measures) rate was 64%. The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5) + etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). Total control (TC; no emetic events, no antiemetic measures, and no nausea) and complete control (CC; no emetic events, no antiemetic measures, and less than mild nausea) were achieved in 51 and 61% of patients, respectively. Logistic regression analysis revealed history of motion sickness, history of pregnancy-associated vomiting and CBDCA-based chemotherapy as risk factors for CR and history of motion sickness and history of pregnancy-associated vomiting as risk factors for TC. Additional, Ages ≥65 years is an independent predictive factor for achieving TC.
Our data showed that two antiemetics were insufficient to control CINV in patients receiving CBDCA- or oxaliplatin-based chemotherapy. However, two antiemetics may be sufficiently effective for elderly male patients receiving CBDCA (AUC5) + ETP, CBDCA+PTX for lung cancer, or CAPOX. Additionally, we consider that three antiemetics are necessary for women with colorectal cancer receiving CAPOX. Risk factor analysis related to CR showed that CINV prophylaxis in patients treated with CBDCA-based chemotherapy was generally supportive of the guideline-recommended three antiemetics. However, the control of nausea in patients receiving non-CBDCA-based chemotherapy is a key point to note. The further individualization of antiemetic regimens for patients receiving MEC based on both types of chemotherapy regimens and sex is needed.
接受中度致吐风险化疗（MEC）的患者中，30%-90%会经历化疗引起的恶心和呕吐（CINV）；然而，最佳的止吐治疗仍存在争议。
在这项针对日本各类癌症接受MEC化疗的成年人的多中心、前瞻性、观察性研究中，入组患者记录CINV日记。所有参与者均接受5-羟色胺-3受体拮抗剂和地塞米松治疗。
在2013年5月至2015年1月入组的400例患者中，386例符合评估条件。中位年龄为64岁（范围26-84岁）。总体完全缓解（CR；无呕吐事件且未采取止吐措施）率为64%。在以卡铂（CBDCA）和奥沙利铂为基础的化疗组中，尤其是女性患者中，达到CR的比例较低。我们发现，在肺癌患者中，男性在CBDCA（AUC5）+依托泊苷（ETP）组（80%）、卡培他滨加奥沙利铂（CAPOX）组（78%）和CBDCA+紫杉醇（PTX）组（73%）中的CR率较高。分别有51%和61%的患者实现了完全控制（TC；无呕吐事件、未采取止吐措施且无恶心）和完全缓解（CC；无呕吐事件、未采取止吐措施且恶心程度小于轻度）。逻辑回归分析显示，晕动病史、妊娠相关呕吐史以及基于CBDCA的化疗是CR的危险因素，晕动病史和妊娠相关呕吐史是TC的危险因素。此外，年龄≥65岁是实现TC的独立预测因素。
我们的数据表明，两种止吐药不足以控制接受基于CBDCA或奥沙利铂化疗患者的CINV。然而，两种止吐药对于接受CBDCA（AUC5）+ETP、CBDCA+PTX治疗肺癌或CAPOX的老年男性患者可能足够有效。此外，我们认为接受CAPOX治疗的结直肠癌女性患者需要三种止吐药。与CR相关的危险因素分析表明，接受基于CBDCA化疗患者的CINV预防总体上支持指南推荐的三种止吐药。然而，接受非CBDCA化疗患者的恶心控制是一个需要注意的关键点。需要根据化疗方案类型和性别对接受MEC治疗的患者的止吐方案进行进一步个体化。
