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Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study

From the Division of Oncology, Department of Medicine, University of Mississippi School of Medicine, Jackson, MS; Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo; Obstetrics and Gynecology, Division of Gynecologic Oncology, Albany Medical Center Hospital, Albany; Department of Obstetrics and Gynecology, University of Rochester School of Medicine, Rochester, NY; Wake Forest University School of Medicine, Winston-Salem, NC; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of California at Irvine Medical Center; and Department of Pathology, University of California at Irvine, Orange, CA

Address reprint requests to Denise Mackey, Gynecologic Oncology Group Administrative Office, Four Penn Center, 1600 John F. Kennedy Blvd, Suite 1020, Philadelphia, PA 19103

PURPOSE: Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone.

PATIENTS AND METHODS: Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m² intravenously or doxorubicin 60 mg/m² plus cisplatin 50 mg/m² every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m² doxorubicin.

RESULTS: There were 12 (8%) complete (CR) and 26 (17%) partial responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and 30 (23%) PRs among patients receiving the combination. The overall response rate was higher among patients receiving the combination (42%) compared with patients receiving doxorubicin (25%; P = .004). Median PFS was 5.7 and 3.8 months, respectively, for the combination and single agent. The PFS hazard ratio was 0.736 (95% CI, 0.577 to 0.939; P = .014). Median OS was 9.0 and 9.2 months, respectively, for the combination and single agent. Overall death rates were similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea, vomiting, and hematologic toxicities were common. The combination produced more grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v 4%), and nausea/vomiting (13% v 3%).

CONCLUSION: Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity. These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma.

Supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (grant No. CA 27469) and the Gynecologic Oncology Group Statistical Office (grant No. CA 37517).

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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