title: Efficacy and safety of rapid escalation of cabergoline in comparison to conventional regimen for macroprolactinoma: A prospective, randomized trial.
abstract: BACKGROUND
  Cabergoline (CAB) is conventionally started at a dose of 0.25-0.5 mg once a week with dose escalation at 1to 3months intervals. Previously, we and others have shown that rapid escalation and high doses of CAB can lead to normalization of serum PRL as early as 8.2 weeks in 93% of the patients. We hypothesize that rapid escalation of CAB doses, may help in both the earlier normalization of PRL and also significant shrinkage of tumor mass.
  
  
  METHODS
  Randomized, prospective, interventional trial.
  
  
  METHODS
  Forty two patients (male or female) with macroprolactinoma were randomized to conventional (group A) or rapid escalation (group B) of CAB dosing. In group B, CAB was started at a dose of 0.5 mg twice a week followed by a weekly hike of 1 mg/week, based on serum PRL and then monthly. The end point of the present study was a composite of normoprolactinemia and tumor shrinkage ≥50% from baseline. PRL and visual field analysis (weekly), other hormonal work up periodically and magnetic resonance imaging (sella) was performed monthly.
  
  
  RESULTS
  A total of 19 patients in each group completed a minimum follow-up of 6 months. There was a reduction of 72.7 ± 26.2% in group A and 84.1 ± 15.0 in group B (P = 0.24) within a week of CAB therapy. The duration of CAB treatment to normalize PRL was 10.2 ± 9.2 week(2-36) in group A and 7.2 ± 6.2 weeks(1-24) in group B (P = 0.28). There was no difference in the tumor shrinkage in either of the groups (92.3% [46.7-100%] in group A and 90.5% [66.6-100%] reduction in group B). The composite end point was achieved in 14 patients in group A (73.6%) and 16 patients in group B (84.2%) (P = 0.69). The composite end point was achieved in 13.1 ± 9.5 weeks (group A) versus 16.5 ± 14.1 weeks (group B) (P = 0.61).
  
  
  CONCLUSIONS
  This is first head to head comparative trial showing that a rapid hike of CAB dose is not associated with earlier normalization of PRL or reduction in tumor volume as compared to conventional monthly hike. There is no difference in the number of patients or duration required to achieve the composite end point. We obtained much earlier PRL normalization (8.4 weeks) as compared to previous studies (36-72 weeks), probably because PRL was not assessed as frequently as in the present study. Rapid escalation of CAB was well tolerated.
  
  
  CONCLUSIONS
  A weekly or a conventional 4 weekly escalation of CAB have a similar efficacy with regards to the achievement of normoprolactinemia and significant tumor shrinkage for macroprolactinoma.
authors.affiliation: Department of Endocrinology, PGIMER, Chandigarh, India.
authors.forename: Ashu
authors.initials: A
authors.lastname: Rastogi
authors.forename: Rama
authors.initials: R
authors.lastname: Walia
authors.forename: Pinaki
authors.initials: P
authors.lastname: Dutta
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
keywords: Rapid escalation; cabergoline; macroprolactinoma
references.citation: J Clin Endocrinol Metab. 1996 Jun;81(6):2338-43
references.pmid: 8964874
references.citation: J Clin Endocrinol Metab. 2000 Jun;85(6):2247-52
references.pmid: 10852458
references.citation: N Engl J Med. 2003 Nov 20;349(21):2035-41
references.pmid: 14627789
references.citation: Indian J Med Res. 2010 Apr;131:530-5
references.pmid: 20424304
references.citation: J Clin Endocrinol Metab. 2008 Dec;93(12):4721-7
references.pmid: 18812485