Greig, C.A., Johns, N., Gray, C., MacDonald, A., Stephens, N.A., Skipworth, R.J., . . . Fearon, K.C. (2014). Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Supportive Care in Cancer, 22, 1269–1275. 

To test the safety, tolerance, and efficacy of an appetite stimulant and an anabolic beta 2 agonist in patients with cancer cachexia

Patients were asked to take formoterol 40 mcg and megestrol 320 mg each morning and 40 mcg formoterol and 160 mg megestrol each evening for eight weeks. Self-reported intake and tablet counts were used to determine patient adherence. Patients were admitted to a clinical research facility on day 1 and discharged after the first dose of study drugs. Patients were contacted by phone after 24 hours for assessment. Additional assessments were done at weeks 2, 4, 6, 8, and 12.

• N = 9 (completed four weeks); 7 (completed eight weeks)  
• MEDIAN AGE = 67 years
• MALES: Not provided, FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: All had advanced disease; specific types were not described.
• OTHER KEY SAMPLE CHARACTERISTICS: Mean weight loss was 11% body weight over the prior five to seven months. 

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Scotland

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Single arm observational

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI's CTCAE) version 3.0
• Body weight
• Maximum isometric knee extensor, lower limb extension, and maximum handgrip strength via dynamometry
• Muscle size measurement via MRI
• Physical activity measured via accelerometry as average daily step count
• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life C30 questionnaire

Patients showed an increase in muscle strength and muscle size. Mean body weight increased by 2.6%. Physical activity increased in three of six patients who responded to treatment. Appetite improved (p = .005). Adverse events were tremor (n = 7), peripheral edema (n = 3), tachycardia (n = 2), and dyspepsia (n = 2).

The combination of megestrol and formoterol may have benefit for patients with cachexia. The sample size of this study was too small to draw conclusions.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Subject withdrawals ≥ 10% 
• Other limitations/explanation: Four patients discontinued possibly due to study drug; 40% overall attrition

The combination of medications tested here may be associated with improved muscle function and appetite in patients with advanced cancer; however, due to the limitations of this study, efficacy and tolerance is not clear. Further well-designed research with these medications is needed to determine efficacy, safety, and tolerance.