Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer

Piccart, M. et al. (2003) Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. International Journal of Gynecological Cancer, 13(s2), pp. 144-148. (doi: 10.1111/j.1525-1438.2003.13357.x)

Abstract

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European–Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin–paclitaxel regimen over cisplatin–cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer. By mid-1993, the Gynecological Oncology Group (GOG) had disclosed the first results of a prospective randomized clinical trial (GOG-111). In this trial, paclitaxel (T) (Taxol®; BMS, Princeton, NJ), combined with cisplatin [(P), given in 1-h combination, denoted as TP], was infused in patients with advanced ovarian cancer for a 24-h period. This regimen produced a higher response rate and a longer progression-free survival (PFS) in women with newly diagnosed and suboptimally debulked FIGO stage III or IV epithelial ovarian cancer than those produced by the standard cyclophosphamide–cisplatin (CP) regimen. A group of European and Canadian investigators found these results to be impressive but not conclusive enough. They believed that: (a) further data were required before the TP combination could be adopted as a new standard first-line chemotherapy regimen for this disease; (b) the TP regimen could be improved by increasing the dose of paclitaxel and shortening its infusion time; and (c) more knowledge was needed regarding the comparative quality of life and economic impacts of these competing regimens. On 1 April 1994, investigators from the European Organization for Research and Treatment of Cancer (EORTC), the Nordic Society of Gynecologic Oncology Cancer (NSGO), the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG), and the Scottish Group joined forces to seek a target accrual of 600 eligible patients. This level of accrual gave this study an 80% probability of detecting an increase in the median PFS by one-third. Accrual of patients in the trial was completed in August 1995, 4 months after GOG publicly reported a highly significant survival advantage in favor of TP and 4 months before these striking results were published in The New England Journal of Medicine. The European–Canadian Intergroup study, referred to as OV-10, differed from the GOG-111 study by including broader criteria for patient selection and recruiting women with optimally debulked stage III or IV disease. This study also enrolled patients having FIGO stage IIB or IIC disease and maintained a flexible center policy concerning secondary surgical interventions, as opposed to the integration of second-look laparotomy in the treatment plan of the GOG-111 study. A further difference was that OV-10 introduced interval debulking surgery as an option in view of the survival advantage associated with this procedure in a randomized clinical trial previously published by the Gynecological Cancer Cooperative Group of the EORTC. Another important difference included the much higher rate of crossover to paclitaxel at the time of first progression following cisplatin–cyclophosphamide in the more recent OV-10 trial, at a time when this new agent became more easily accessible.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paul, Mr James and Cassidy, Professor James
• Authors: Piccart, M., Bertelsen, K., Stuart, G., Cassidy, J., Mangioni, C., Simonsen, E., James, K., Kaye, S., Vergote, I., Blom, R., Grimshaw, R., Atkinson, R., Swenerton, K., Trope, C., Nardi, M., Kaern, J., Tumolo, S., Timmers, P., Roy, J., Lhoas, F., Lidvall, B., Bacon, M., Birt, A., Andersen, J., Zee, B., Paul, J., Pecorelli, S., Baron, B., and Mcguire, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: International Journal of Gynecological Cancer
• Publisher: Lippincott Williams & Wilkins
• ISSN: 1048-891X