Appetite Stimulants Progestational Agents

Megestrol acetate and medroxyprogesterone acetate are synthetic progestagens that also have some mineralocorticoid activity. Megestrol acetate has been favoured and is one of the most studied therapies in cancer cachexia [80]. Originally used as a therapy in hormone-sensitive tumours, the observation that in a substantial number of patients appetite and weight increased led to it being studied in cancer cachexia [81]. It has been widely promoted as a therapy for cachexia and anorexia, although whether patient function or quality of life is improved is less clear. Appetite can be increased after only a short period of treatment [82]. Improvements in well-being may also occur in some patients without obvious changes in nutritional status [83]. Although it has not been assessed in all studies, there appears to be little impact on lean body mass, which is currently thought to be the most important body compartment in modulating function. In fact, a detrimental effect on muscle has been demonstrated in elderly males [84] and the weight gain seems largely secondary to increased fat and some fluid [85]. This is consistent with observations in AIDS patients [86, 87]. Megestrol acetate has also been shown to induce male hypogonadism [88] and there are theoretical reasons as to why this may not be beneficial to cachectic cancer patients.

Although megestrol acetate may improve general well-being [83], there is conflicting evidence of its impact on quality of life [89-91]. Whilst the progestagens seem to be quite well tolerated (it is possible that in some cases this may reflect brief study duration), there have been concerns over increased risks of thromboembolic disease (TED). There is also a possibility of adrenal suppression in some patients [92, 93]. The interaction of prog-estational agents with chemotherapy requires further study [94] and the benefits of combining them with other agents or resistance exercise remain to be established. It is unclear how these drugs exert their effects but they may modulate cytokines [95], insulin-like growth factor [96], or neuropeptides [97]. While it is not possible to advocate the generalised use of these agents on the available data, certain carefully selected patients, particularly those with significant anorexia, may benefit from them. The possible increase in TED should inform patient selection and counselling. The potential for tumour progression in some patients should also be borne in mind [98]. Whether progestagens should be combined with testosterone or specialised nutrition, for example, remains to be determined, as does optimum dosing and duration of therapy [99].

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