Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group.
OBJECTIVE
We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy.


METHODS
Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer.


RESULTS
The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001).


CONCLUSIONS
We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.
London Gynaecological Oncology Group, The Royal Marsden National Health Service Trust, United Kingdom. m.gore@icr.ac.uk
M
M
Gore
P
P
Mainwaring
R
R
A'Hern
V
V
MacFarlane
M
M
Slevin
P
P
Harper
R
R
Osborne
J
J
Mansi
P
P
Blake
E
E
Wiltshaw
J
J
Shepherd
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016190:Carboplatin