title: Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These data suggest that combination treatment with cabergoline and pegvisomant is more effective at reducing IGF-I levels than either cabergoline or pegvisomant monotherapy.
authors.affiliation: Department of Endocrinology, Christie Hospital, Wimslow Road, Manchester M20 4BX, United Kingdom.
authors.forename: C E
authors.initials: CE
authors.lastname: Higham
authors.forename: A B
authors.initials: AB
authors.lastname: Atkinson
authors.forename: S
authors.initials: S
authors.lastname: Aylwin
authors.forename: M
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: W M
authors.initials: WM
authors.lastname: Drake
authors.forename: A
authors.initials: A
authors.lastname: Lewis
authors.forename: N M
authors.initials: NM
authors.lastname: Martin
authors.forename: V
authors.initials: V
authors.lastname: Moyes
authors.forename: J
authors.initials: J
authors.lastname: Newell-Price
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016903:Drug Monitoring; D004351:Drug Resistance / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004873:Ergolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D006113:United Kingdom
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000077465:Cabergoline; C406545:pegvisomant