Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study.
OBJECTIVE
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.


METHODS
Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m(2) intravenously or doxorubicin 60 mg/m(2) plus cisplatin 50 mg/m(2) every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m(2) 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%).


CONCLUSIONS
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.
Thigpen
J Tate
JT
Division of Oncology, Department of Medicine, University of Mississippi School of Medicine, Jackson, USA.
Brady
Mark F
MF
Homesley
Howard D
HD
Malfetano
John
J
DuBeshter
Brent
B
Burger
Robert A
RA
Liao
Shu
S
D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced
D004317:Doxorubicin; D002945:Cisplatin