Abstract

Abstract Background

This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia‐cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer‐associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.

To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia‐cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.

We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.

Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia‐cachexia syndrome related to cancer, AIDS or any other underlying pathology.

Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.

We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta‐analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.

This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

Author(s)

Vicente Ruiz Garcia, Eduardo López‐Briz, Rafael Carbonell Sanchis, Jose Luis Gonzalvez Perales, Sylvia Bort‐Martí

Abstract

Plain language summary

Megestrol acetate for treatment of anorexia‐cachexia syndrome

Anorexia‐cachexia syndrome (ACS) is a common clinical problem characterised by loss of appetite and weight loss. It is common in patients who suffer from advanced cancer, AIDS and some other conditions. At present, there is no cure for ACS.

Megestrol acetate (MA) is classified as a female hormone and is taken by mouth. It is currently used to improve appetite and to increase weight in ACS.

This updated review shows that:

‐ MA improves appetite and has a small effect on weight gain;

‐ MA does not improve quality of life;

‐ side effects are more frequent in patients treated with MA.

This review shows that MA is associated with an increased risk of blood clots (which may result in swelling, pain or redness of one extremity and not the other, sudden difficulty in breathing, severe headache or vision changes), fluid retention (resulting in swelling of the feet or hands) and death.

In patients who take MA, approximately one in four will have an increase in their appetite, one in 12 will have an increase in their weight and one in 23 will die.

Limited data are available regarding the safety of using MA, especially in the long term. 

Author(s)

Vicente Ruiz Garcia, Eduardo López‐Briz, Rafael Carbonell Sanchis, Jose Luis Gonzalvez Perales, Sylvia Bort‐Martí

Reviewer's Conclusions

Authors' conclusions

Implications for practice

The new trials identified and included in the present review update have not led to significant changes to the conclusions of the previous review (megestrol acetate (MA) improves appetite and slightly increases weight, without clinical relevance), except for adverse events. MA may be prescribed in patients with cancer to increase appetite and improve weight gain. Currently, there is no evidence to recommend MA to improve quality of life. This update has followed The Cochrane Collaboration guidelines for an unbiased review. Quality is difficult to define, since it depends on the design, conduct and analysis of a trial, its clinical relevance or the quality of reporting. Studies of low methodological quality can alter the interpretation of the benefit of an intervention. In this update, we assessed 58% of the trials as high quality for some outcomes such as improvement of weight.

Many concerns remain unresolved. Health‐related quality of life is an important goal in health care and cancer clinical trials, and is the cornerstone for delivery of good palliative medicine. The increasing recognition of patient autonomy means that subjective measures will become more important and, in the current climate of evidence‐based medicine, such measures must be valid and reliable.

Despite MA being approved US Food and Drug Administration for use in AIDS patients, this drug failed to show weight improvement and weight gain when compared with other drugs. MA compared with placebo was effective in AIDS patients in one trial.

In summary, MA could be prescribed to improve appetite in the context of palliative medicine, but it should be emphasised that this drug will probably not lead to full weight loss recovery or improve quality of life, and it is related to adverse events, including an increased risk of death.

Implications for research

This update of the review shows that there is still a need for high‐quality trials focused on the evaluation of the effectiveness of MA. Trials with long‐term follow‐up are needed to rule out an increase in mortality. Even though the US Food and Drug Administration has approved MA for use in AIDS patients, more research is needed in this respect.