Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.
OBJECTIVE
On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens.


METHODS
Eligible patients were randomly allocated to receive cisplatin 50 mg/m(2) every 3 weeks (CPT); cisplatin 50 mg/m(2) day 1 plus topotecan 0.75 mg/m(2) days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m(2) days 1, 15, and 22, vinblastine 3 mg/m(2) days 2, 15, and 22, doxorubicin 30 mg/m(2) day 2, and cisplatin 70 mg/m(2) day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately.


RESULTS
The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively.


CONCLUSIONS
This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.
Long
Harry J
HJ
Mayo Clinic College of Medicine, Rochester, MN, USA.
Bundy
Brian N
BN
Grendys
Edward C
EC
Benda
Jo Ann
JA
McMeekin
D Scott
DS
Sorosky
Joel
J
Miller
David S
DS
Eaton
Lynne A
LA
Fiorica
James V
JV
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011788:Quality of Life; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage* / Q000633:toxicity; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014747:Vinblastine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014747:Vinblastine; D019772:Topotecan; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate