Treatment of Prolactin-Secreting Pituitary Macroadenomas with the Long-acting Non-Ergot Dopamine Agonist CV 205-502

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Abstract
The study objective was the evaluation of the effects of an experimental long-acting non-ergot dopamine agonist, CV 205-502, on serum prolactin, tumor size, gonadal function, visual abnormalities, and tolerability in patients with macroprolactinomas. It was designed as a prospective study, unblinded, dose escalation used as needed. Four university medical centers; patients referred for treatment was used as the setting. Twenty-six hyperprolactinemic patients (prolactin > 150 .mu.g/L) with a pituitary macroadenoma were treated for 24 weeks with CV 205-502 given once daily. Serum prolactin was measured at regular intervals. Prolactin levels decreased in all patients during treatment (mean pretreatment level, 2051.7 .+-. 1077 .mu.g/L [.+-. SE]; 24 weeks, 39.0 .+-. 11.3 .mu.g/L; P = 0.0001); normal prolactin levels were achieved in 15 (58%). Tumor size decreased in 21 or 26 patients and ranged from 6% to 67% (mean, 19.2% .+-. 3.4%). Onset or return of regular menses occurred in 11 of 15 premenopausal women, accompanied by an increase in estradiol concentrations (pretreatment, 186.5 .+-. 25.0 pmol/L; on treatment, 690.9 .+-. 104.3 pmol/L; P = 0.0003). Serum testosterone increased in 6 of 8 men; sexual function improved in 5 of 7 with pretreatment abnormalities. Two patients with reversible visual abnormalities improved within 2 weeks of starting treatment. Side effects occurred in 11 patients and abated over 1 to 2 weeks or after the dose was reduced. There was no evidence of toxicity as indicated by serial serum chemistries, liver function tests, hematologic profiles, thyroxine levels, and electrocardiogram studies. CV 205-502 reverses hyperprolactinemia and promotes reduction in tumor size with reversal of visual abnormalities and restoration of gonadal function in most patients. This compound will probably be useful in treating prolactinomas.