Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials

Abstract

Summary The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin-or carboplatinbased therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than nonplatinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.Keywords: meta-analysis; systematic review; randomized controlled trials; advanced ovarian cancer; chemotherapy Health care professionals and patients alike are becoming increasingly aware of the need to make medical decisions on the basis of up-to-date, objective and unbiased research (Chalmers and Haynes, 1994). The most reliable information results from randomized controlled trials (RCTs). Unfortunately, most RCTs, including those conducted in ovarian cancer, have been too small to demonstrate moderate treatment benefits with reliability, and many results have been inconclusive or contradictory. The Advanced Ovarian Cancer Trialists Group (AOCTG) recognized that the best means of synthesizing such randomized evidence is by systematic meta-analysis. In 1988, five meta-analyses of chemotherapy in advanced ovarian cancer using updated individual patient data were initiated. The first results were published in 1991 (AOCTG, 1991). The AOCTG recognized the importance of updating these results especially for the comparison of carboplatin and cisplatin, in which the data were relatively immature. The comparison of platinum analogues was considered of such clinical importance that further new investigations were initiated to identify whether any particular type of women or tumour would benefit more from either cisplatin-or carboplatin-based chemotherapy. PATIENTS AND METHODSTrials were eligible for inclusion provided they examined first-line chemotherapy for advanced ovarian cancer, were properly randomized and made one of the treatment comparisons described below. Trials were identified by bibliographic searches using MEDLINE and CancerLit, by hand searching relevant meeting proceedings and by consulting trial registers (AOCTG, 1991). Both published and unpublished trials were included and updated data were sought for all randomized patients. All data were checked thoroughly and the final database entries for each trial were verified by the responsible trialist or data centre.All analyses were based on intention to treat. Survival analyses were stratified by trial, and t...

LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential

“…First-line therapy constitutes optimal surgical debulking followed by administration of a platinum-based regimen. 144 Unfortunately, approximately 60-80% of patients relapse after initial treatment, and develop cisplatin resistance. 145,146 As such, Chang et al studied the ability of LB100 to sensitize ovarian cancer to cisplatin treatment using known cisplatin-resistant, p53-null (SKOV-3, OVCAR-8) cell lines as well as patient-derived cell lines harvested both prior to and after clinical development of cisplatin resistance.…”

Use of CA-125 in Clinical Trial Evaluation of New Therapeutic Drugs for Ovarian Cancer

“…Carboplatin proved equally efficacious (in single and combination therapy) but significantly less toxic than cisplatin (5). At standard doses, carboplatin has fewer adverse effects on kidneys, the nervous system, or the auditory system, and patients who receive carboplatin report reductions in nausea and vomiting relative to levels experienced with cisplatin.…”

“…Although no hard evidence for an overall survival advantage with platinum-based compounds was demonstrated until the 1990s (4,5), early studies revealed that cisplatin significantly improved disease-free survival and response rates when compared with then-standard treatments. Cisplatin was effective as a single agent and in combination regimens, resulting in the relatively popular first-line combination of cisplatin with cyclophosphamide.…”

Cancer of the ovary, fallopian tube, and peritoneum

“…Patients who have had primary cytoreduction should receive chemotherapy following surgery [1,51] (Table 3). The accepted standard is 6 cycles of platinum-based combination chemotherapy, with a platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel) [52][53][54][55][56].…”