A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study.
OBJECTIVE
After surgical debulking and volume-directed irradiation of the pelvis/para-aortic lymph nodes, treatment was randomized to compare recurrence-free survival (RFS) and toxicity between two chemotherapy regimens for the treatment of women with advanced stage endometrial carcinoma.


METHODS
Treatment was randomized between 6 cycles of cisplatin [C] (50 mg/m(2)) and doxorubicin [D] (45 mg/m(2)) with or without paclitaxel [P] (160 mg/m(2)). Initially in paclitaxel treated patients and, after May 2002, all patients received granulocyte growth factor with each cycle.


RESULTS
Of 659 patients enrolled following surgery, 552 eligible patients were randomized to chemotherapy after irradiation. Accrual closed to Stage IV patients in June, 2003. Approximately 80% completed six cycles of chemotherapy. Three deaths resulted from bowel complications and one death was due to renal failure. Hematologic adverse events, sensory neuropathy and myalgia, were more frequent and severe in the paclitaxel arm (p<0.01) which was confirmed by Quality of Life assessments. Percentage of patients alive and recurrence-free at 36 months was 62% for CD vs. 64% for CDP. The hazard of recurrence or death relative to the CD arm stratified by stage is 0.90 (95% CI is 0.69 to 1.17, p=0.21, one-tail). However, in subgroup analysis, CDP was associated with a 50% reduction in the risk of recurrence or death among patients with gross residual disease (95% CI: 0.26 to 0.92). Stage, residual disease, histology/grade, positive para-aortic node and cytology, pelvic metastases and age were significantly associated with RFS.


CONCLUSIONS
The addition of paclitaxel to cisplatin and doxorubicin following surgery and radiation was not associated with a significant improvement in RFS but was associated with increased toxicity.
Homesley
Howard D
HD
Brody School of Medicine, Room 2S-12, Division of Gynecologic Oncology, Leo Jenkins Cancer Center, Greenville, NC 27834, USA. hdh7173@aol.com
Filiaci
Virginia
V
Gibbons
Susan K
SK
Long
Harry J
HJ
Cella
David
D
Spirtos
Nick M
NM
Morris
Robert T
RT
DeGeest
Koen
K
Lee
Roger
R
Montag
Anthony
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011878:Radiotherapy / Q000379:methods
D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin