EFFECT OF THE NEW DOPAMINERGIC AGONIST CV 205-502 ON PLASMA PROLACTIN LEVELS AND TUMOR SIZE IN BROMOCRIPTINE-RESISTANT PROLACTINOMAS

Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10% and to reduce tumour size in one-third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long-term effects of bromocriptine and CV 205-502 (a non-ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine-resistant prolactinomas. Bromocriptine reduced significantly (P < 0.001) plasma prolactin levels (from 2307 +/- 518 to 568 +/- 279-mu-g/1) (conversion to Sl units: 1-mu-g/1 = 20 mU/1). Visual field defects observed in five patients improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side-effects at the beginning of the treatment, CV 205-502 was well tolerated in five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205-502 and it was necessary to reduce the daily dose. CV 205-502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205-502 was more potent than bromocriptine as demonstrated by the further 90% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205-502 treatment. However, no further change in visual disturbance or in tumour size was observed during the treatment with CV 205-502. These results show that CV 205-502 appears to be more potent than bromocriptine in reducing plasma prolactin levels in some bromocriptine-resistant prolactinomas and suggest that different mechanisms may be involved in such a resistance.