The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers , suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia .
Ghrelin is a hormone with multiple physiologic functions , including promotion of growth hormone release , stimulation of appetite and regulation of energy homeostasis .
Treatment with ghrelin/ghrelin-receptor agonists is a prospect i ve therapy for disease-related cachexia and malnutrition .
In vitro studies have shown high expression of ghrelin in cancer tissue , although its role including its impact in cancer risk and progression has not been established .
Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials.
BACKGROUND Patients with advanced cancer frequently experience anorexia and cachexia , which are associated with reduced food intake , altered body composition , and decreased functionality . We assessed anamorelin , a novel ghrelin-receptor agonist , on cachexia in patients with advanced non-small-cell lung cancer and cachexia . METHODS ROMANA 1 and ROMANA 2 were r and omised , double-blind , placebo-controlled phase 3 trials done at 93 sites in 19 countries . Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia ( defined as ≥5 % weight loss within 6 months or body-mass index < 20 kg/m(2 ) ) were r and omly assigned 2:1 to anamorelin 100 mg orally once daily or placebo , with a computer-generated r and omisation algorithm stratified by geographical region , cancer treatment status , and weight loss over the previous 6 months . Co- primary efficacy endpoints were the median change in lean body mass and h and grip strength over 12 weeks and were measured in all study participants ( intention-to-treat population ) . Both trials are now completed and are registered with Clinical Trials.gov , numbers NCT01387269 and NCT01387282 . FINDINGS From July 8 , 2011 , to Jan 28 , 2014 , 484 patients were enrolled in ROMANA 1 ( 323 to anamorelin , 161 to placebo ) , and from July 14 , 2011 , to Oct 31 , 2013 , 495 patients were enrolled in ROMANA 2 ( 330 to anamorelin , 165 to placebo ) . Over 12 weeks , lean body mass increased in patients assigned to anamorelin compared with those assigned to placebo in ROMANA 1 ( median increase 0·99 kg [ 95 % CI 0·61 to 1·36 ] vs -0·47 kg [ -1·00 to 0·21 ] , p<0·0001 ) and ROMANA 2 ( 0·65 kg [ 0·38 to 0·91 ] vs -0·98 kg [ -1·49 to -0·41 ] , p<0·0001 ) . We noted no difference in h and grip strength in ROMANA 1 ( -1·10 kg [ -1·69 to -0·40 ] vs -1·58 kg [ -2·99 to -1·14 ] , p=0·15 ) or ROMANA 2 ( -1·49 kg [ -2·06 to -0·58 ] vs -0·95 kg [ -1·56 to 0·04 ] , p=0·65 ) . There were no differences in grade 3 - 4 treatment-related adverse events between study groups ; the most common grade 3 - 4 adverse event was hyperglycaemia , occurring in one ( < 1 % ) of 320 patients given anamorelin in ROMANA 1 and in four ( 1 % ) of 330 patients given anamorelin in ROMANA 2 . INTERPRETATION Anamorelin significantly increased lean body mass , but not h and grip , strength in patients with advanced non-small-cell lung cancer . Considering the unmet medical need for safe and effective treatments for cachexia , anamorelin might be a treatment option for patients with cancer anorexia and cachexia . FUNDING Helsinn Therapeutics
The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers , suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia .
Ghrelin is a hormone with multiple physiologic functions , including promotion of growth hormone release , stimulation of appetite and regulation of energy homeostasis .
Treatment with ghrelin/ghrelin-receptor agonists is a prospect i ve therapy for disease-related cachexia and malnutrition .
In vitro studies have shown high expression of ghrelin in cancer tissue , although its role including its impact in cancer risk and progression has not been established .