© The Author 2006. Published by Oxford University Press.
ARTICLE |
Survival Benefits With Diverse Chemotherapy Regimens for Ovarian Cancer: Meta-analysis of Multiple Treatments
Affiliations of authors: Department of Obstetrics and Gynaecology, Hammersmith Hospital, Queen Charlotte's and Chelsea Hospital, London, U.K. (MK); Department of Obstetrics and Gynaecology, University Hospital of Ioannina, Ioannina, Greece (MK, EP); Medical Research Council, Biostatistics Unit, Cambridge, U.K. (GS); Division of Medical Oncology, University of Ioannina School of Medicine, Ioannina, Greece (NP); Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (JPAI); Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece (JPAI); Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts University School of Medicine, Boston, MA (JPAI)
Correspondence to: John P. A. Ioannidis, MD, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece (e-mail: jioannid{at}cc.uoi.gr).
Background: Numerous randomized trials have compared different chemotherapy regimens in women with ovarian cancer. Although ovarian cancer survival has improved in recent years, the magnitude of these incremental benefits across diverse regimens is unclear. Methods: We used multiple-treatment meta-analysis methodology to combine information from direct and indirect comparisons of all chemotherapy regimens used in randomized trials of ovarian cancer in the last 40 years. Chemotherapy was categorized by the use or not of platinum and/or taxanes, combinations of agents, and intraperitoneal administration. Monte Carlo simulations were used to determine which regimen most improved survival. Analyses of trials that examined first- and second-line treatments were also performed separately. Results: We found 198 trials (N = 38 440 women) involving 120 different chemotherapy regimens published in 1971–2006. Eighty-two trials compared different types of chemotherapy, among which 60 had usable survival information (N = 15 609 women). Monte Carlo simulations showed a 92% probability that the regimen that best prolonged survival is a platinum and taxane combination with intraperitoneal administration; this regimen resulted in a 55% relative risk reduction (95% confidence interval [CI] = 39% to 67%) for mortality as compared with nonintraperitoneal monotherapy using neither platinum nor taxane. Against that same monotherapy comparator, platinum-based combinations with and without intraperitoneal administration achieved 40% (95% CI = 21% to 54%) and 30% (95% CI = 20% to 38%) relative risk reductions for mortality, respectively, and combinations involving platinum and taxane without intraperitoneal administration achieved a 42% (95% CI = 31% to 51%) relative risk reduction. Results were similar when analyses were limited to first-line treatment. Data on second-line treatment were consistent with the superiority of platinum and taxane combinations. Conclusions: Distinct incremental improvements in survival have been achieved for ovarian cancer chemotherapy over time, with the possibility to achieve a doubling or more of time to mortality with platinum and taxane combinations, especially when intraperitoneal administration is used.
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