Yuka Ito, Hiroko Minatogawa, and Sayaka Kano, St Marianna University School of Medicine Hospital; Takashi Tsuda, Koichiro Tsugawa, Yasuyuki Kojima, Naoki Furuya, Kunihiro Matsuzaki, Mamoru Fukuda, and Takako Eguchi Nakajima, St Marianna University School of Medicine; Ayako Tsuboya, Kawasaki Municipal Tama Hospital, Kawasaki; Kentaro Sakamaki and Takeharu Yamanaka, Yokohama City University School of Medicine; Sadatoshi Sugae and Ichiro Ohta, Yokohama City University Hospital; Hitoshi Arioka, Yokohama Rosai Hospital; Kazutaka Narui, Yokohama City University Medical Center, Yokohama; Masahiko Ando, Nagoya University Hospital, Nagoya; Yutaka Tokuda, Tokai University School of Medicine, Kanagawa; Takashi Suda, Takahata Public Hospital, Takahata-Chou; Satoshi Morita, Graduate School of Medicine, Kyoto University, Kyoto; and Narikazu Boku, National Cancer Center Hospital, Tokyo, Japan.
J Clin Oncol. 2018 Apr 1;36(10):1000-1006. doi: 10.1200/JCO.2017.74.4375. Epub 2018 Feb 14.
Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK-RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK-RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at -15.0% (Arm D1 - Arm D3). Results A total of 396 patients-196 and 200 patients in Arms D3 and D1, respectively-were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, -12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, -8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, -14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK-RA and Palo in HEC.
目的 我们评估了在高度致吐性化疗（HEC）中，与连续 3 天使用地塞米松（DEX）相比，第 1 天使用 DEX 并在第 2 和第 3 天进行剂量节约，同时联合使用神经激肽-1 受体拮抗剂（NK-RA）和帕洛诺司琼（Palo）的非劣效性。
方法 计划接受 HEC（顺铂≥50mg/m 或蒽环类药物加环磷酰胺）的患者被随机分配接受连续 3 天使用 DEX（Arm D3）或第 1 天使用 DEX，第 2 和第 3 天使用安慰剂（Arm D1），联合使用 NK-RA 和帕洛诺司琼。主要终点是完全缓解（CR），定义为整个（0 至 120 小时）阶段无呕吐和无解救药物。非劣效性边界设定为-15.0%（Arm D1-Arm D3）。
结果 共评估了 396 例患者，分别为 Arm D3 组 196 例和 Arm D1 组 200 例。整个期间的 CR 率分别为 Arm D3 组的 46.9%和 Arm D1 组的 44.0%（95%CI，-12.6%至 6.8%；P=0.007）。急性（0 至 24 小时）阶段的 CR 率分别为 Arm D3 组的 63.3%和 Arm D1 组的 64.5%（95%CI，-8.1%至 10.6%；P<0.001），延迟（24 至 120 小时）阶段的 CR 率分别为 Arm D3 组的 56.6%和 Arm D1 组的 51.5%（95%CI，-14.8%至 4.6%；P=0.023）。在 Arm D3 组中，第 4 天和第 5 天作为 DEX 相关不良反应观察到更多的热潮红和震颤，而在 Arm D1 组中，第 2 天和第 3 天观察到更多的厌食、抑郁和疲劳。作为生活质量的一个指标，总体健康状况在两组中相似。
结论 在 HEC 中，联合使用 NK-RA 和帕洛诺司琼时，可以在第 2 和第 3 天节约 DEX 的使用。
