Efficacy and safety of rapid escalation of cabergoline in comparison to conventional regimen for macroprolactinoma: A prospective, randomized trial

Introduction: 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.

Study design: Randomized, prospective, interventional trial.

Subjects and 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).

Discussion: 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.

Conclusion: 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.