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were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths.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...

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Insulin tolerance tests were carried out in six depressed patients before and after administration of mebanazine and in six before and after administration of phenelzine. There was no change in fasting blood glucose with treatment, but glucose levels after insulin were significantly lower during treatment with both these hydrazine MAOI's. There was no effect on the changes in pulse, blood pressure and sweating in response to hypoglycemia. The hypoglycemic action of mebanazine was further investigated in five patients from a diabetic clinic who were poorly controlled on sulfonylurea treatment and who were not depressives. Glucose tolerance was improved in all cases five weeks after addition of mebanazine, 20 mg. daily to the regime, and there was a significant (p = 0.031) reduction in blood glucose at all times of the glucose tolerance test. The mean glucose tolerance of four patients showed deterioration after discontinuation of mebanazine. Glucose tolerance did not improve in five patients treated with placebo. Insulin sensitivity of depressed patients was increased during administration of hydrazine MAOI's and a hypoglycemic action in diabetes was demonstrable in the absence of a depressive illness.

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1. A method is described for measuring glucose uptake by pieces of human skeletal muscle removed at surgery.2. Glucose uptake by this preparation was stimulated by insulin (0.1-10 munits/ml) and inhibited by 2.27 mM-sodium n-butyrate in the presence of insulin (0.1 munit/ml).3. The antidiabetic drug metformin (60.4 ,UM) had no effect on glucose uptake in the absence or presence of insulin (0.1 munit/ml), but stimulated uptake in the presence of 2-27 mM-sodium n-butyrate together with insulin (0.1 munitlml). It is concluded that the metabolic control of glucose uptake in human skeletalmuscle is similar to that in rat heart and diaphragm, and that the preparation provides a useful model for biochemical and pharmacological investigations of glucose metabolism in skeletal muscle.

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