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    Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial.

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    Authors
    Higham, Claire E
    Atkinson, A
    Aylwin, S
    Bidlingmaier, M
    Drake, W
    Lewis, A
    Martin, N
    Moyes, V
    Newell-Price, J
    Trainer, Peter J
    Affiliation
    Department of Endocrinology (C.E.H., P.J.T.), Christie Hospital, Manchester M20 4BX, United Kingdom
    Issue Date
    2012-01-25
    
    Metadata
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    Abstract
    Context:With adequate dose titration, pegvisomant normalizes IGF-I in up to 97% of patients with acromegaly. Pegvisomant is indicated for treatment-resistant disease but is expensive, particularly at a high dose. It has been used successfully in combination with somatostatin analogs. However, there are no therapeutic reports of pegvisomant in combination with dopamine agonists. Cabergoline is orally active, well-tolerated, and relatively inexpensive, and as monotherapy for acromegaly it is reported to normalize IGF-I in up to 30% of patients.Objective:The aim of the study was to investigate the efficacy of cabergoline monotherapy and pegvisomant in combination with cabergoline to control serum IGF-I in patients with active acromegaly. Twenty-four patients were recruited into a United Kingdom, multicenter, open-label, prospective clinical trial.Main Outcome Measure:We measured the change in serum IGF-I.Results:After 18 wk of dose titration to a maximum dose of 0.5 mg once daily, cabergoline monotherapy did not significantly reduce IGF-I (454 ± 219 baseline vs. 389 ± 192 ng/ml cabergoline), although two patients did normalize IGF-I. The addition of 10 mg pegvisomant daily for 12 wk significantly reduced IGF-I (389 ± 192 ng/ml cabergoline vs. 229 ± 101 ng/ml combination), and 68% achieved a normal IGF-I. Twelve weeks after cabergoline withdrawal, while continuing to receive pegvisomant 10 mg, only 26% of patients maintained an IGF-I within the reference range (229 ± 101 ng/ml combination vs. 305 ± 177 ng/ml pegvisomant). There were no significant changes in liver transaminases or glucose metabolism throughout the study.Conclusion:These data suggest that combination treatment with cabergoline and pegvisomant is more effective at reducing IGF-I levels than either cabergoline or pegvisomant monotherapy.
    Citation
    Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial. 2012,97(4):1187-1193 J Clin Endocrinol Metab
    Journal
    Journal of Clinical Endocrinology and Metabolism
    URI
    http://hdl.handle.net/10541/221556
    DOI
    10.1210/jc.2011-2603
    PubMed ID
    22278424
    Type
    Article
    Language
    en
    ISSN
    1945-7197
    ae974a485f413a2113503eed53cd6c53
    10.1210/jc.2011-2603
    Scopus Count
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