Pitfalls in placebo-controlled trials in palliative care: dexamethasone for the palliation of malignant bowel obstruction

Abstract

To determine the effect of dexamethasone when treating malignant bowel obstruction, 35 patients were randomized to receive intravenous dexamethasone or a placebo, crossing over to the alternate treatment arm if there had been no resolution of obstruction by day 5. This was done in two consecutive studies. Patients were stratified according to whether or not they had received specific anticancer therapy within 28 days of study. In trial 1, 15 out of 22 patients 'responded' (resolution of obstruction by day 5; 10 on dexamethasone, five on placebo). Eleven out of 15 patients were 'on treatment'. In trial 2, six out of 13 responded (three on dexamethasone, three on placebo); three out of six were 'on treatment'. When both studies are combined, 60% (21/35) patients responded (13 on dexamethasone, eight on placebo). Poor patient accrual terminated both studies. Numbers are too small to allow a combination of studies or formal statistical analysis. We are unable to make any conclusion as to the effectiveness of dexamethasone in the palliation of malignant bowel disease.

Current concepts in malignant bowel obstruction management

“…Small uncontrolled trials have reported benefi t from corticosteroids [41], but the most effective type, dose, dosing regimen, and route of administration have not been clarifi ed. A 2008 Cochrane review identifi ed seven retrospective and two unpublished reports containing three randomized, double-blind, controlled trials of 89 patients [42] (Laval et al, personal communication, 1998). Cochrane reviewers concluded that corticosteroids may reduce bowel obstruction in patients with GI and ovarian cancers, with low rates of adverse effects.…”

Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer

“…From the morbidity data described in Hardy (Hardy 1997a;Hardy 1997b) it was not possible to distinguish morbidity due to the drug as opposed to the underlying condition. No data were supplied comparing placebo to the treatment group.…”

“…It was also the smallest study in terms of size. Hardy (Hardy 1997a;Hardy 1997b) stratified the patients into those who had recently received chemotherapy and those who had not. Laval 1998 did not do this analysis.…”

“…Two unpublished reports containing three randomised, placebo, double blind controlled trials (a total of 89 patients) were obtained (Hardy 1997a;Hardy 1997b;Laval 1998) by personal contact via the Association of Palliative Medicine and International Organisations of Palliative Medicines respectively. Seven retrospective and prospective reports were also located, (two reports via Medline, one report via Embase, two reports via hand searching and two reports via personal contact).…”

Role of Steroids in Malignant Bowel Obstruction

“…Hardy et al 11 reported a randomized double blind placebo controlled trial in patients with gynecological cancer. He observed bowel obstruction resolution in 13 of 35 patients with 4 mg intravenously dexamethasone given every 6 hours (total 16 mg/ day) for 5 days.…”