A randomised trial investigating the dose intensity of primary chemotherapy in patients with ovarian carcinoma: a comparison of chemotherapy given every four weeks with the same chemotherapy given at three week intervals.
BACKGROUND
The dose intensity of chemotherapy for patients with ovarian carcinoma remains a controversial issue. Few randomised trials have been conducted examining dose intensity using the same total dose of chemotherapy. This study was designed to investigate two schedules of chemotherapy using standard and higher dose intensity with both groups receiving the same total dose.


METHODS
Patients with FIGO stage IC, II, III and IV epithelial ovarian carcinoma were randomised to receive cycles of cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with doxorubicin (50 mg/ m2) and ifosfamide (5 g/m2) at either four-weekly (n = 47) or three-weekly (n = 97) intervals (1:2 randomisation). At randomisation patients were stratified according to histological grade and amount of post operative residual tumour (greater or less than 2 cm). The two arms of the study were well balanced in terms of the major prognostic features.


RESULTS
There was no difference in either progression free survival or overall survival between the two arms. The median overall survival was 730 days for the three-weekly treatment and 740 days in the four-weekly arm (progression-free survival was 500 days and 483 days, respectively). The combined overall response rate (complete and partial response) in the 114 assessable patients was 65.7% (66.7% for the three-weekly treatment and 64% for the four-weekly treatment). These differences were not statistically different.


CONCLUSIONS
A modest increase in the dose intensity of chemotherapy (1:3 fold) failed to improve the response rate, progression-free survival and overall survival in patients with ovarian carcinoma.
CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK.
E
E
Wrigley
A
A
Weaver
G
G
Jayson
M
M
Ranson
J
J
Renninson
J
J
Prendiville
M
M
Dobson
C D
CD
Collins
R
R
Swindell
C H
CH
Buckley
J A
JA
Radford
D
D
Crowther
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015996:Survival Rate; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D007069:Ifosfamide