Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Division of Biostatistics, Department of Clinical Medicine, Kitasato University School of Pharmacy, Tokyo, Japan.
JAMA Oncol. 2019 Jun 1;5(6):833-840. doi: 10.1001/jamaoncol.2019.0001.
The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer; however, it has not been assessed in postoperative adjuvant chemotherapy for endometrial cancer.
To evaluate the clinical benefit of taxane plus platinum compared with standard doxorubicin plus cisplatin as postoperative adjuvant chemotherapy in endometrial cancer.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, open-label, phase 3 randomized clinical trial, patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had 2 cm or greater residual tumor were included from 118 institutions in Japan from November 24, 2006, to January 7, 2011. Data was analyzed from March 15, 2017, to June 30, 2017.
Eligible patients were randomly assigned (1:1:1) to receive 6 cycles of doxorubicin, 60 mg/m2, plus cisplatin, 50 mg/m2, on day 1; docetaxel, 70 mg/m2, plus cisplatin, 60 mg/m2, on day 1; or paclitaxel, 180 mg/m2, plus carboplatin (area under the curve, 6.0 mg/mL × min) on day 1 every 3 weeks.
The primary end point was progression-free survival. Secondary end points were overall survival, occurrence of adverse events, tolerability, and status of lymph node dissection.
Among 788 eligible patients, the median (SD) age was 59 (22-74) years; 263 patients were assigned to doxorubicin plus cisplatin treatment, 263 patients to docetaxel plus cisplatin treatment, and 262 patients to paclitaxel plus carboplatin treatment. The number of patients who did not complete 6 cycles was 53 (20.1%) for the doxorubicin plus cisplatin group, 45 (17.1%) for the docetaxel plus cisplatin group, and 63 (24.0%) for the paclitaxel plus carboplatin group. Tolerability of these regimens were not statistically different. After a median follow-up period of 7 years, there was no statistical difference of progression-free survival (doxorubicin plus cisplatin, 191; docetaxel plus cisplatin, 208; paclitaxel plus carboplatin, 187; P = .12) or overall survival (doxorubicin plus cisplatin, 217; docetaxel plus cisplatin, 223; paclitaxel plus carboplatin, 215; P = .67) among the 3 groups. The 5-year progression-free survival rate was 73.3% for the doxorubicin plus cisplatin group, 79.0% for the docetaxel plus cisplatin group, and 73.9% for the paclitaxel plus carboplatin group, while the 5-year overall survival rates were 82.7%, 88.1%, and 86.1%, respectively.
There was no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer. Because each regimen showed adequate tolerability but different toxic effects, taxane plus platinum regimens may be a reasonable alternative to treatment with doxorubicin plus cisplatin.
UMIN-CTR identifier: UMIN000000522.
重要性：紫杉烷类加铂类方案已被证明对晚期或复发性子宫内膜癌有效；然而，它在子宫内膜癌术后辅助化疗中的作用尚未得到评估。
目的：评估与标准多柔比星加顺铂相比，紫杉烷类加铂类作为子宫内膜癌术后辅助化疗的临床获益。
设计、地点和参与者：这是一项多中心、开放性、III 期随机临床试验，纳入了来自日本 118 家机构的高危 I 期或 II 期或 III 期或 IV 期且未超出腹腔、肿瘤残留>2cm 的子宫内膜癌患者，入组时间为 2006 年 11 月 24 日至 2011 年 1 月 7 日。数据分析时间为 2017 年 3 月 15 日至 2017 年 6 月 30 日。
干预措施：符合条件的患者被随机分为三组（1:1:1），分别接受 6 个周期的多柔比星 60mg/m2 加顺铂 50mg/m2（第 1 天）；多西他赛 70mg/m2 加顺铂 60mg/m2（第 1 天）；或紫杉醇 180mg/m2 加卡铂（曲线下面积 6.0mg/mL×min）（第 1 天），每 3 周一次。
主要终点和次要终点：主要终点是无进展生存期。次要终点是总生存期、不良事件发生情况、可耐受性和淋巴结清扫情况。
结果：在 788 名符合条件的患者中，中位（标准差）年龄为 59（22-74）岁；263 名患者被分配至多柔比星加顺铂治疗组，263 名患者被分配至多西他赛加顺铂治疗组，262 名患者被分配至紫杉醇加卡铂治疗组。有 53 名（20.1%）患者未完成 6 个周期的治疗，多柔比星加顺铂组 45 名（17.1%），多西他赛加顺铂组 45 名（17.1%），紫杉醇加卡铂组 63 名（24.0%）。这些方案的耐受性无统计学差异。中位随访 7 年后，3 组患者的无进展生存期（多柔比星加顺铂组 191 例，多西他赛加顺铂组 208 例，紫杉醇加卡铂组 187 例，P=0.12）或总生存期（多柔比星加顺铂组 217 例，多西他赛加顺铂组 223 例，紫杉醇加卡铂组 215 例，P=0.67）均无统计学差异。3 组患者的 5 年无进展生存率分别为多柔比星加顺铂组 73.3%、多西他赛加顺铂组 79.0%和紫杉醇加卡铂组 73.9%，5 年总生存率分别为 82.7%、88.1%和 86.1%。
结论和相关性：多柔比星加顺铂、多西他赛加顺铂或紫杉醇加卡铂作为子宫内膜癌术后辅助化疗，患者的生存无显著差异。由于每种方案均具有足够的耐受性但毒性作用不同，紫杉烷类加铂类方案可能是多柔比星加顺铂治疗的合理替代方案。
试验注册：UMIN-CTR 标识符：UMIN000000522。
