Trial Information

Efficacy of Rapid Escalation of Cabergoline in Comparison to Conventional Dosing in Prolactin Secreting Macroadenomas.

The efficacy of cabergoline is dose related and determined by percentage of Dopamine 2
receptor occupancy and prolonged receptor affinity. Activation of membrane receptors and
target cell responses is proportional to the degree of receptor occupancy. Greater the drug
concentration, greater is the binding and receptor occupancy and greater is the efficacy of
the drug. Receptor occupancy can be increased either by using high dose of cabergoline or by
rapid escalation of cabergoline. The patients, who respond to increasing dosages of
cabergoline, probably do so by increased receptor occupancy with higher doses.

Rapid escalation of doses of cabergoline is another approach to increase the drug
concentration and increase the occupancy of the receptor. Earlier decrease in serum
prolactin levels with rapid escalation may help in reducing the cumulative dose of
cabergoline and total duration of treatment. Though studies with high doses of cabergoline
have been performed in prolactinomas with normalization of prolactin levels in almost 100%,
but systematic studies using rapid escalation of cabergoline in prolactinomas are lacking
except the one by Bhansali et al. In their study, serum prolactin became normal in 93 per
cent of the patients with a mean duration of 8.2 wk. The mean decrease in serum prolactin
was 99 per cent by four weeks, however a similar decrease (93 to 99%) in prolactin was
achieved in other studies with a time lag of 48 to 160 wk. This supports the notion that
rapid hike in doses of cabergoline decreases serum prolactin levels faster and it becomes
normal in the majority of patients earlier6. However it was an uncontrolled study with
limited number of subjects.

Therefore present study was planned to study the efficacy of rapid escalation of Cabergoline
versus conventional dosing in patients with macroprolactinomas. Rapid escalation of
cabergoline dose may help in earlier normalization of prolactin and shrinkage of tumor mass,
and thus decrease the cumulative dose of cabergoline altogether.