Abstract: We screened 926 individual references and identified three studies that satisfied the inclusion criteria. Fifty-nine participants (37 men and 22 women) aged between 54 and 78 years were randomised initially, 47 participants completed the treatment. One study had a parallel design and two had a cross-over design. The studies included people with a variety of cancers and also differed in the dosage, route of administration, frequency and duration of treatment. One trial, which compared ghrelin with placebo, found that ghrelin improved food intake (very low-quality evidence) and had no adverse events (very low-quality evidence). Due to unavailability of data we were unable to report on comparisons for ghrelin versus no treatment or alternative experimental treatment modalities, or ghrelin in combination with other treatments or ghrelin analogues/ghrelin mimetics/ghrelin potentiators. Two studies compared a higher dose of ghrelin with a lower dose of ghrelin, however due to differences in study designs and great diversity in the treatment provided we did not pool the results. In both trials, food intake did not differ between participants on higher-dose and lower-dose ghrelin. None of the included studies assessed data on body weight. One study reported higher adverse events with a higher dose as compared to a lower dose of ghrelin. All studies were at high risk of attrition bias and bias for size of the study. Risk of bias in other domains was unclear or low. We rated the overall quality of the evidence for primary outcomes (food intake, body weight, adverse events) as very low. We downgraded the quality of the evidence due to lack of data, high or unclear risk of bias of the studies and small study size. There is insufficient evidence to be able to support or refute the use of ghrelin in people with cancer cachexia. Adequately powered randomised controlled trials focusing on evaluation of safety and efficacy of ghrelin in people with cancer cachexia is warranted.

Plain-language summary: We found three studies that recruited a total of 59 cancer patients (37 men and 22 women) aged between 54 and 78 years. Forty-seven cancer patients completed the treatment. Studies differed in study design and included people with a variety of cancers. Studies also differed in dosage, route of injection, frequency and duration of treatment. One study compared ghrelin with a placebo while two studies compared different doses of ghrelin (higher dose with lower dose). Outcomes of interest to cancer patients with loss of appetite and weight loss, such as improvement in food intake and improvement in body weight, were not adequately reported. All three included studies were funded by government agencies. One study received an additional grant from a pharmaceutical company. We found insufficient evidence that using ghrelin demonstrated differences in food intake. We found no evidence that using ghrelin alone or in combination made any difference to body weight. We could not reach any conclusions about its side effects. The limited amount of information means that we could not draw any conclusions. We rated the quality of evidence from studies using four levels: high, moderate, low, or very low. High-quality evidence means that we are very confident in the results. Very low-quality evidence means that we are very uncertain about the results. The evidence in this review was of very low quality.