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Original Investigation
March 21, 2019

Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
  • 2Division of Biostatistics, Department of Clinical Medicine, Kitasato University School of Pharmacy, Tokyo, Japan
  • 3Department of Gynecology, Aichi Cancer Center Hospital, Aichi, Japan
  • 4Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan
  • 5Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Kanagawa, Japan
  • 6Department of Gynecology, Niigata Cancer Center Hospital, Niigata, Japan
  • 7Department of Obstetrics and Gynecology, Kurume University School of Medicine, Fukuoka, Japan
  • 8Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Iwate, Japan
  • 9Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan
  • 10Department of Gynecology, Tohoku University Hospital, Miyagi, Japan
  • 11Department of Gynecology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Tokyo, Japan
  • 12Division of Obstetrics and Gynecology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Miyagi, Japan
  • 13Clinical Research, Innovation and Education Center, Tohoku University Hospital, Miyagi, Japan
  • 14Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
  • 15Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan
JAMA Oncol. 2019;5(6):833-840. doi:10.1001/jamaoncol.2019.0001
Key Points

Question  Will taxane plus platinum regimens show superiority over standard doxorubicin plus cisplatin in postoperative adjuvant chemotherapy treatment of patients with high-risk early stage or optimally debulked advanced-stage endometrial cancer?

Findings  This multicenter, phase 3 randomized clinical trial provides an analysis of progression-free survival in 788 patients on postoperative taxane plus platinum regimens, including docetaxel plus cisplatin or paclitaxel plus carboplatin, as compared with doxorubicin plus cisplatin. Taxane plus platinum regimens did not demonstrate a survival benefit over doxorubicin plus cisplatin, though they were well tolerated and had different profiles of toxicities from that of doxorubicin plus cisplatin.

Meaning  This study indicates that taxane plus platinum regimens can be an alternative to doxorubicin plus cisplatin in adjuvant chemotherapy for patients with endometrial cancer that has risk factors for progression.

Abstract

Importance  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.

Objective  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.

Interventions  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.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

Trial Registration  UMIN-CTR identifier: UMIN000000522

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