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

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Abstract

Purpose

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.

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Acknowledgments

We thank the study participants and to Claire Lamb (RGN) and staff of the Clinical Research Facility, Royal Infirmary Edinburgh, UK.

Disclosures

This work was supported by Acacia Pharma Ltd. GF is the Chief Medical Officer of Acacia Pharma Ltd. There are no other conflicts of interest.

Author information

Authors and Affiliations

  1. School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh, EH16 4SB, UK

    C. A. Greig, N. Johns, A. MacDonald, N. A. Stephens, R. J. E. Skipworth & K. C. H. Fearon

  2. Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, EH16 4SB, UK

    C. Gray

  3. Department Clinical Oncology, Western General Hospital, Edinburgh, EH4 2XU, UK

    L. Wall

  4. Centre for Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK

    M. Fallon

  5. Acacia Pharma Ltd., Harston Mill, Cambridge, CB22 7GG, UK

    G. M. Fox

  6. Department of Clinical Surgery, Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK

    K. C. H. Fearon

Authors
  1. C. A. Greig
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  2. N. Johns
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  3. C. Gray
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  4. A. MacDonald
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  5. N. A. Stephens
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  6. R. J. E. Skipworth
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  7. M. Fallon
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  8. L. Wall
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  10. K. C. H. Fearon
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Corresponding author

Correspondence to K. C. H. Fearon.

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Greig, C.A., Johns, N., Gray, C. et al. Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Support Care Cancer 22, 1269–1275 (2014). https://doi.org/10.1007/s00520-013-2081-3

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  • DOI: https://doi.org/10.1007/s00520-013-2081-3

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