Effective Combination Treatment with Cabergoline and Low-Dose Pegvisomant in Active Acromegaly: A Prospective Clinical Trial

• Published in: The journal of clinical endocrinology and metabolism 2012-04, Vol.97 (4), p.1187-1193
• Main Authors: Higham, C. E, Atkinson, A. B, Aylwin, S, Bidlingmaier, M, Drake, W. M, Lewis, A, Martin, N. M, Moyes, V, Newell-Price, J, Trainer, P. J
• Format: Article
• Language: English
• Subjects: Acromegaly - blood; Acromegaly - drug therapy; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Dopamine Agonists - administration & dosage; Dopamine Agonists - adverse effects; Dopamine Agonists - therapeutic use; Drug Monitoring; Drug Resistance - drug effects; Drug Therapy, Combination - adverse effects; Endocrinopathies; Ergolines - administration & dosage; Ergolines - adverse effects; Ergolines - therapeutic use; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Human Growth Hormone - administration & dosage; Human Growth Hormone - adverse effects; Human Growth Hormone - analogs & derivatives; Human Growth Hormone - blood; Human Growth Hormone - therapeutic use; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin-Like Growth Factor I - analysis; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Patient Dropouts; Receptors, Somatotropin - antagonists & inhibitors; United Kingdom; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-2603

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.