To summarise the evidence from scientific studies on cancer anorexia-cachexia syndrome in order to assess and highlight the efficacy of high-dose progestins, i.e. megestrol acetate (MA) and medroxyprogesterone acetate (MPA), compared with placebo, in patients with hormone-independent tumours.

MEDLINE, Cancerlit, EMBASE and CINAHL were searched using the following keywords: 'anorexia', 'cachexia', 'progestins', 'megestrol acetate', 'medroxyprogesterone acetate', 'neoplasm', 'random allocation' and 'randomised clinical trial/study'. Studies published in any language and any year were considered. Additional studies were identified by handsearching relevant sources, examining reference lists, and by contacting experts.

Study designs of evaluations included in the review

Only prospective randomised studies were included in the review. These could be open or blind.

Specific interventions included in the review

To be included, trials had to have a placebo control arm and one or more treatment arms using the progestins MA or MPA. Doses for MA ranged from 160 to 1600 mg/day, whilst doses for MPA ranged from 300 to 1000 mg/day.

Participants included in the review

For a trial to be included, the study population had to include patients with a proven diagnosis of advanced hormone-independent tumour, with a decrease in appetite and/or weight loss. Patients also had to be capable of taking oral therapy.

Outcomes assessed in the review

The primary outcome measures were appetite and body weight. The authors decided to analyse these variables as dichotomous data. Therefore, differences in appetite and body weight between the baseline and end point for each trial were categorised as a 'yes' or 'no' change.

How were decisions on the relevance of primary studies made?

Two reviewers independently made the decisions on whether to include or exclude the studies.

Although validity was not systematically assessed, some methodological factors (e.g. blinding and a sample size calculation) appeared in the data extraction tables.

Two reviewers independently extracted the data from the included studies.

Data were extracted on the following: author and reference; setting; study design; whether a sample size calculation was performed; the method of randomisation; eligibility criteria; concomitant therapy; characteristics of the patients; the mean age (with standard deviation) of the participants; drug dose; treatment duration; outcomes; the instruments used to measure outcomes; follow-up; the number of patients (total and per arm); the number of drop-outs, withdrawals and protocol deviations; the results for weight and appetite; side-effects; and other outcomes favouring treatment.

How were the studies combined?

The dichotomous outcomes for each study were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The pooled OR and 95% CIs were estimated using the random-effects model of DerSimonian and Laird (see Other Publications of Related Interest no.1).

How were differences between studies investigated?

Heterogeneity between trials was evaluated using both an exact test and a visual display in a L'Abbe plot (see Other Publications of Related Interest no.2).

Fifteen studies (2,102 randomised patients) were included in the systematic review.

Weight gain.

Dichotomous data for weight gain were available from 11 trials. The pooled OR for weight gain was 2.66 (95% CI: 1.80, 3.92), favouring high-dose progestins over placebo. The L'Abbe plot and exact test showed that no gross statistical heterogeneity existed in the results of these trials (p=0.172). The analysis of the 5 trials that excluded the administration of any form of antiblastic treatment, even with purely palliative intent, showed a very similar OR estimate of 2.73 (95% CI: 1.27, 5.85).

Appetite.

Dichotomous data for appetite were available from 6 trials. The pooled OR from these trials was 4.23 (95% CI: 2.53, 7.04), favouring high-dose progestins. The heterogeneity between studies was not statistically significant (p=0.250). The analysis of the 4 studies that enrolled patients who had not undergone concurrent treatments, gave a pooled OR of 5.90 (95% CI: 3.39, 10.27).

The effects of high-dose progestins on appetite and body weight were clearly demonstrated. However, further studies are undoubtedly warranted to investigate other aspects of progestin activity, especially with regards to dosage, duration and timing with best therapeutic index.

This systematic review was conducted according to well-defined criteria and good methodology. A range of sources were searched for relevant material, without restrictions on the publication date or language. Two reviewers independently selected papers for the review using criteria based on the study design, treatment and participants. Details of the included studies were appropriately presented in tabular format and the outcome data were appropriately combined. Heterogeneity was statistically assessed. Although aspects of study design that might have influenced the outcomes were presented in tables, a systematic validity assessment was not conducted.

The authors' conclusions were supported by the results of the review.

Practice: The authors did not state any implications for practice.

Research: The authors state that 'further studies are undoubtedly warranted to investigate other aspects of progestin activity, especially as regards dosage, duration and timing with best therapeutic index'.

1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. 2. L'Abbe KA, Detsky AS, O'Rourke K. Meta-analysis in clinical research. Ann Intern Med 1987;107:224-33.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.