Beta-hydroxy beta-methylbutyrate/arginine/glutamine (HMB/Arg/Gln) supplementation to improve the management of cachexia in patients with advanced lung cancer: an open-label, multicentre, randomised, controlled phase II trial (NOURISH)

Abstract

Background Cancer cachexia causes significant morbidity and mortality in advanced lung cancer patients. Clinical benefit of β-hydroxy-β-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) was assessed in newly diagnosed patients. Methods NOURISH, a prospective, two-arm, open-label, multi-centre, randomised controlled phase II trial compared cachexia in patients who received HMB/Arg/Gln with those who did not. All patients received structured nutritional, exercise and symptom control via a Macmillan Durham Cachexia Pack. Conducted in five UK centres, patients aged > 18 years, with newly diagnosed advanced small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), who were able to take oral nutrition, with a performance status of 0-to-2 and a life expectancy > 4 months were eligible for trial entry. Patients suitable for treatment with curative intent were ineligible. The trial was designed as a signal-seeking pilot study with target recruitment of 96 patients. One-to-one randomisation was stratified by diagnosis (SCLC or NSCLC), stage of disease (locally advanced or metastatic) and performance status. The primary outcome measure was treatment success defined as a patient being alive without significant loss of lean body mass (not > 5%) by 12 weeks. Secondary outcome measures included quality of life. Results Between February-2012 and February-2013, 38 patients were recruited, 19 to each arm. Baseline characteristics were balanced. The trial was halted due to slow accrual and partial adherence. Trial data demonstrated no evidence of treatment benefit. No serious adverse events were reported during the trial. Conclusions Further evaluation of HMB/Arg/Gln in this setting could not be recommended on the basis of this trial. Clinical trial registration ISRCTN registry: 39911673; 14-Apr-2011 10.1186/ISRCTN39911673.

Effect of Megestrol Acetate Combined With Oral Nutrition Supplement in Malnourished Lung Cancer Patients: A Single-Center Prospective Cohort Study

“…Combined medical therapy using MA and fish oil, dronabinol, or NSAIDs resulted in no changes in weight or appetite compared to MA alone ( 21 , 22 ). Beta-hydroxy beta-methyl butyrate/arginine/glutamine(HMB/Arg/Gln) may work together to decrease muscle damage from reactive oxygen species and pro-inflammatory cytokine; however, recent data demonstrated that HMB/Arg/Gln supplementation couldn't improve the loss of lean body mass in patients with advanced lung cancer ( 23 ).…”

Therapeutic Potential of Glutamine Pathway in Lung Cancer

“…However, other investigators have also found that modulating Gln intake in patients with lung cancer may result in different outcomes. Jennifer Pascoe et al evaluated Beta-hydroxy betamethylbutyrate/arginine/glutamine (HMB/Arg/Gln) in newly diagnosed lung cancer patients, but ultimately found that HMB/Arg/Gln reduced the odds of treatment success, contrary to the hypothesis (93). Gln did not demonstrate a corresponding effect on radiotherapy-induced esophagitis in the study by Abdul Rahman Jazieh et al consistently, which may be due to the specific combination of chemotherapeutic agents or inappropriate doses of Gln (86).…”

Dietary Supplements in People with Metastatic Cancer Who Are Experiencing Malnutrition, Cachexia, Sarcopenia, and Frailty: A Scoping Review

“…The 48 articles were classified into the following categories: full text peer-reviewed manuscripts (n = 38), conference abstracts (n = 8), and clinical trial registrations (n = 2). Of the full text peer-reviewed manuscripts, the majority reported on randomized controlled trials (RCTs) (n = 18) [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], followed by quasi-experimental trials (n = 15) [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66], retrospective cohort observational studies (n = 2) [67,68], and case studies (n = 3) [69][70][71]. Conference abstracts reported on RCTs (n = 3) [72][73][74], quasi-experimental trials (n = 4) [75][76][77][78], and a case study (n = 1) [79].…”

“…Arginine was the main dietary supplement investigated in an RCT where it was administered in the form of a specially formulated enteral formula and replaced 41% of casein [36], as well as in an observational study where it was given in the form of an immunonutrition enteral formula (Impact ® ) containing 12.5 g/L L-arginine, dietary nucleotides, EPA, and docosahexaenoic acid (DHA) [67]. Arginine was investigated as part of a combined treatment with glutamine (amino acid) and β-hydroxyl β-methyl butyrate (HMB) (amino acid metabolite) in three studies (two RCTs [35,45] and one quasi-experimental trial [57]), which were also the only studies where glutamine or HMB were included. Daily doses were in the following ranges: 14-28 g arginine, 14-28 g glutamine, and 2.4-6 g HMB daily [35,45,57].…”

“…Arginine was investigated as part of a combined treatment with glutamine (amino acid) and β-hydroxyl β-methyl butyrate (HMB) (amino acid metabolite) in three studies (two RCTs [35,45] and one quasi-experimental trial [57]), which were also the only studies where glutamine or HMB were included. Daily doses were in the following ranges: 14-28 g arginine, 14-28 g glutamine, and 2.4-6 g HMB daily [35,45,57].…”