Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy

作者:Greig C A; Johns N; Gray C; MacDonald A; Stephens N A; Skipworth R J E; Fallon M; Wall L; Fox G M; Fearon K C H*
来源:Supportive Care in Cancer, 2014, 22(5): 1269-1275.
DOI:10.1007/s00520-013-2081-3

摘要

Purpose The aim of this study was to test the safety, tolerability and efficacy of a novel combination of an anabolic beta(2)-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 mu g/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.

  • 出版日期2014-5