title: Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy.
abstract: OBJECTIVE
  The aim of this study was to test the safety, tolerability and efficacy of a novel combination of an anabolic β2-agonist and an appetite stimulant in patients with cancer cachexia.
  
  
  METHODS
  Thirteen patients (M/F 5:8) with advanced malignancy and involuntary weight loss received oral formoterol (80 μg/day) and megestrol acetate (480 mg/day) for up to 8 weeks. Quadriceps size (MRI), quadriceps and hand-grip strength, lower limb extensor power, physical activity and quality of life were measured at baseline and at 8 weeks. Response criteria were specified pre-trial, with a major response defined as an increase in muscle size ≥ 4 % or function ≥ 10 %.
  
  
  RESULTS
  Six patients withdrew before 8 weeks, reflecting the frail, comorbid population. In contrast, six out of seven (86 %) patients completing the course achieved a major response for muscle size and/or function. In the six responders, mean quadriceps volume increased significantly (left 0.99 vs. 1.05 L, p=0.012; right 1.02 vs. 1.06 L, p=0.004). There was a trend towards an increase in quadriceps and handgrip strength (p>0.05). The lack of appetite symptom score declined markedly (76.2 vs. 23.8; p=0.005), indicating improvement. Adverse reactions were few, the commonest being tremor (eight reports), peripheral oedema (three), tachycardia (two) and dyspepsia (two).
  
  
  CONCLUSIONS
  In this frail cohort with advanced cancer cachexia, an 8-week course of megestrol and formoterol in combination was safe and well tolerated. Muscle mass and/or function were improved to a clinically significant extent in most patients completing the course. This combination regimen warrants further investigation in larger, randomized trials.
authors.affiliation: School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh, EH16 4SB, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Greig
authors.forename: N
authors.initials: N
authors.lastname: Johns
authors.forename: C
authors.initials: C
authors.lastname: Gray
authors.forename: A
authors.initials: A
authors.lastname: MacDonald
authors.forename: N A
authors.initials: NA
authors.lastname: Stephens
authors.forename: R J E
authors.initials: RJ
authors.lastname: Skipworth
authors.forename: M
authors.initials: M
authors.lastname: Fallon
authors.forename: L
authors.initials: L
authors.lastname: Wall
authors.forename: G M
authors.initials: GM
authors.lastname: Fox
authors.forename: K C H
authors.initials: KC
authors.lastname: Fearon
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000188:drug therapy / Q000209:etiology; D000886:Anthropometry / Q000379:methods; D019167:Appetite Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D003131:Combined Modality Therapy; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008535:Megestrol / Q000009:adverse effects / Q000627:therapeutic use*; D019290:Megestrol Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D015431:Weight Loss / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D019167:Appetite Stimulants; D004983:Ethanolamines; D008535:Megestrol; D019290:Megestrol Acetate; D000068759:Formoterol Fumarate