Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.
BACKGROUND
A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial.


METHODS
This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided.


RESULTS
The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen.


CONCLUSIONS
There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.
Piccart
M J
MJ
European Organization for Research and Treatment of Cancer (EORTC)-Gynecological Cancer Cooperative Group, EORTC Data Center, Brussels, Belgium. mpiccart@ulb.ac.be
Bertelsen
K
K
James
K
K
Cassidy
J
J
Mangioni
C
C
Simonsen
E
E
Stuart
G
G
Kaye
S
S
Vergote
I
I
Blom
R
R
Grimshaw
R
R
Atkinson
R J
RJ
Swenerton
K D
KD
Trope
C
C
Nardi
M
M
Kaern
J
J
Tumolo
S
S
Timmers
P
P
Roy
J A
JA
Lhoas
F
F
Lindvall
B
B
Bacon
M
M
Birt
A
A
Andersen
J E
JE
Zee
B
B
Paul
J
J
Baron
B
B
Pecorelli
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin