日本一项关于大剂量顺铂同步放化疗用于头颈部鳞状细胞癌的多中心I/II期研究。
Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan.
作者信息
Matsuyama Hiroshi, Yamazaki Keisuke, Okabe Ryuichi, Ueki Yushi, Shodo Ryusuke, Omata Jo, Sato Yuichiro, Ota Hisayuki, Takahashi Takeshi, Tomita Masahiko, Yokoyama Yusuke, Togashi Takafumi, Aoyama Hidefumi, Abe Eisuke, Saijo Yasuo, Katsura Kouji, Soga Marie, Sugita Tadashi, Matsumoto Yasuo, Tsuchida Emiko, Horii Arata
机构信息
Departments of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Departments of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
出版信息
Auris Nasus Larynx. 2018 Oct;45(5):1086-1092. doi: 10.1016/j.anl.2018.02.008. Epub 2018 Mar 19.
OBJECTIVE
Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese.
METHODS
Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m for level 0, 80mg/m for level 1, and 100mg/m for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m, response rate, and incidences of adverse events.
RESULTS
A CDDP dose of 100mg/m was the MTD for phase I, and the recommended dose for phase II was 80 mg/m. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event.
CONCLUSION
The present phase I study indicated that a CDDP dose of 80mg/m is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m as compared with a dose of 100mg/m, and a dose of 80mg/m is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).
目的
近期数据表明，使用高剂量顺铂（CDDP）的同步放化疗（CCRT）是晚期头颈部鳞状细胞癌（SCC）最有效的治疗方法。关于CDDP的剂量，西方国家最推荐的是100mg/m²。然而，在疗效和不良事件的平衡方面，不同种族中细胞毒性药物（如CDDP）的合适剂量可能有所不同。在这项多中心I/II期研究中，我们旨在确定日本晚期头颈部SCC患者CCRT中CDDP的最佳剂量。
方法
如果患者患有头颈部SCC，并接受包括对原发灶及双侧II-IV级淋巴结进行全颈照射的根治性CCRT，则符合纳入标准。在I期研究中，CDDP剂量0级为70mg/m²，1级为80mg/m²，2级为100mg/m²。通过I期试验检查最大耐受剂量（MTD）和剂量限制性毒性（DLT），据此确定II期的CDDP剂量。II期的主要终点是CCRT完成率，次要终点是全剂量CCRT完成率、接受总CDDP剂量≥200mg/m²的患者百分比、缓解率和不良事件发生率。
结果
I期的MTD是100mg/m²，II期的推荐剂量是80mg/m²。47例患者在II期试验中接受评估。CCRT完成率、全剂量CCRT率以及接受总CDDP剂量≥200mg/m² 的患者百分比分别为93.6%、78.7%和93.6%。1例患者（2.1%）出现2级肾功能不全，无患者出现发热性中性粒细胞减少或4级不良事件。
结论
目前的I期研究表明，就安全性而言，80mg/m² 的CDDP剂量是最佳剂量。II期研究显示，与100mg/m² 的剂量相比，80mg/m² 的CDDP剂量在CCRT完成率、缓解率和不良事件发生率方面并不逊色，因此在日本患者的CCRT中推荐80mg/m² 的剂量。本研究已在大学医院医学信息网络临床试验注册中心（UMIN-CTR；识别号UMIN000010369）注册。
Zotero 插件