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were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths.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...
Summary Specimens from 45 patients with previously-untreated non-small cell lung cancer (NSCLC) were tested for in vitro chemosensitivity to ten drugs utilising the DiSC assay, which measures cell kill in the total (largely non-dividing) tumour cell population. Thirty-five assays were successful and 25 patients with advanced disease subsequently received chemotherapy with the 'best' three drugs selected by the assay. Six patients were Karnofsky performance status 60 or less and the median pretreatment weight loss was 8.5%. Nine patients had a partial response (response rate = 36%; 95% confidence interval = 17-55%) and the median survival of all patients was 202 days. Specimens from responding patients were significantly more sensitive in the assay to drugs in general (especially to etoposide and to 'natural product' drugs) and to the drugs used in treatment than were specimens from non-responding patients. In vitro drug resistance differences between responding and non-responding patients were of greater significance than were differences between other clinical and laboratory measurements. Assay results classified patients into two cohorts, having relatively high and low probabilities of responding to chemotherapy. Assay results also identified patient cohorts with above average and below average durations of survival. Five patients (20%) were found to have tumours with extreme drug resistance (EDR), defined as assay results for the average of all ten tested drugs falling greater than one standard deviation more resistant than the median for all tumours assayed, and none of these patients with EDR responded to chemotherapy.No single program of chemotherapy has emerged as the standard of treatment for patients with advanced non-small cell lung cancer (NSCLC). Randomised comparisons have covered a ranged of options including multidrug and single drug therapy and no chemotherapy (Mulshine et al., 1986;Hansen, 1987). Therapeutic choice has often been without significant impact on survival. Where statistically significant survival improvement has been reported the magnitude of the benefit has been modest and caution seems appropriate in weighing this benefit vs the toxicity from the treatment.One hope for improving treatment outcome has been the provision of customised treatment on the basis of individual tumour properties. From December 1983 through August 1986 we investigated this approach with a pilot study of individualised chemotherapy for NSCLC selected on the basis of an in vitro drug resistance assay. The assay chosen was a dye exclusion assay (the DiSc Assay) which has received extensive study in haematologic neoplasms (Weisenthal et al., 1984;Weisenthal et al., 1986;Bird et al., 1985;Bosanquet et al., 1983;Bird et al., 1986;Tidefelt et al., 1989;Kirkpatrick et al., 1990;Lathan et al., 1990;Bosanquet, 1991), but more preliminary evaluation in solid tumours Gazdar et al., 1990).We are now reporting the final results of this trial.
There is a lack of consensus regarding optimal surgical management of symptomatic pericardial effusions in patients with malignancies. Subxiphoid pericardial window formation (subxiphoid pericardial drainage) has been considered a safe and effective method for diagnostic and therapeutic purposes. To ensure adequate drainage, many surgeons prefer the formation of a larger pericardial window by performing either an anterior thoracotomy or a partial/total pericardiectomy. To evaluate the efficacy of these methods for palliation of symptomatic pericardial effusion in patients with malignancy, 28 consecutive pericardial surgery cases involving patients with malignancy were retrospectively analyzed. Ten patients (Group 1) had subxiphoid window formation, whereas 18 patients (Group 2) had partial or total pericardiectomy or pericardial window formation by anterior thoracotomy. There was no statistically significant difference (P = 0.22) in the survival rates between these two groups. A median survival time of 2.67 months (range, 0.43 to 26.6 months) was observed in Group 1 versus 1.23 months (range, 0.03 to 10.83 months) in Group 2. However, a statistically significant difference (P less than or equal to 0.02) in postoperative morbidity was observed between the two groups: 67% in Group 2 versus 10% in Group 1. Because of lower morbidity, subxiphoid pericardial window formation is recommended by this study as the preferred surgical method for palliation of symptomatic pericardial effusion in patients with malignancy.
One hundred and six patients (103 solid tumors, three lymphomas) were treated with large infrequent doses of mitomycin C. Thirteen patients in this group received combined radiation and chemotherapy and were evaluated separately. Most patients received 50 mg of the drug in a divided dose during the first week of treatment. After 6 weeks, maintenance injections of 10 to 30 mg of the drug were given to responsive patients at 4‐ to 6‐week intervals. Twenty‐two per cent of the patients showed a 50% reduction in tumor mass for a month or longer. Patients with breast and gastrointestinal carcinoma responded most frequently. The remission rates and durations are similar to those of published studies using other dosage schedules. Toxic effects have been similar though possibly less frequent. There appears to be no therapeutic advantage in using large infrequent doses of the drug; however, the time‐saving to both patient and medical staff has been significant.
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