Hiura, Y., Takiguchi, S., Yamamoto, K., Takahashi, T., Kurokawa, Y., Yamasaki, M., . . . Doki, Y. (2012). Effects of ghrelin administration during chemotherapy with advanced esophageal cancer patients: A prospective, randomized, placebo-controlled phase 2 study. Cancer, 118, 4785–4794.

To examine the effects of administration of synthetic ghrelin on appetite and oral intake in patients with advanced esophageal cancer during chemotherapy

Patients were randomized to receive either ghrelin at 3 µg/kg over 30 minutes twice daily or placebo for seven consecutive days (days 1–7 of therapy) intravenously. All patients also received the same protocol of IV fluid of 3 L/day from days 1–3 and 2 L/day from days 4–7. Appetite was scored prior to each meal. A registered dietitian determined caloric intake by measuring the weight of each dish before and after every meal.

• The study reported on a final sample of 40 patients.
• Mean patient age was 63.4 years.
• The sample was 87.5% male and 12.5% female.
• All patients had stage II or higher esophageal disease. All were receiving cisplatin-based chemotherapy.

• Single site 
• Inpatient setting
• Japan

Patients were undergoing active antitumor treatment.

The study was a placebo-controlled randomized controlled trial.

• Appetite visual analog scale (VAS)
• Caloric intake
• Rapid turnover protein levels: prealbumin, transferrin
• Common Terminology Criteria for Adverse Events

Dietary intake declined after cisplatin administration to the lowest levels on days 5–7. It took another 4–7 days for oral intake to recover and enable discharge from the hospital. The decline in dietary intake was less in the ghrelin group (p = 0.0027). On day 7, intake with ghrelin was 26.7 kcal/kg/day compared to 23.1 kcal/kg/day for those receiving placebo. Prealbumin was higher in those on ghrelin (p = 0.042), and transferrin was higher with ghrelin (p = 0.037) compared to those levels in the placebo group. The severity grades of anorexia and nausea were lower with ghrelin (< 0.02).

Findings suggest that administration of ghrelin during cisplatin-based chemotherapy was effective in reducing anorexia and maintaining caloric intake compared to placebo.

• The study had a small sample size, with less than 100 participants.
• Lack of blinding had an associated risk of bias.
• Unintended interventions or applicable interventions were not described that would influence results.
• The intervention was expensive, impractical, or required training.
• The use of antiemetics during treatment was not described, so it is unclear whether there were differences between groups that could have affected outcomes.
• Although findings were statistically significant, the actual difference in caloric intake appears to be fairly small.
• The sample included only patients who had no previous chemotherapy, and physicians had discretion to exclude patients based on no particular criteria. It is unclear whether this could have produced sample bias. 
• This protocol would only be feasible in an inpatient setting.

Findings suggest that ghrelin as administered in this study may be beneficial to preserve appetite and nutritional intake during chemotherapy.  As done here, ghrelin and fluid administration would only be practical in an inpatient setting.