Efficacy of quinagolide in resistance to dopamine agonists: results of a multicenter study. Club de l'Hypophyse.

OBJECTIVE: A retrospective French multicenter analysis was carried out to assess changes in tumor volume and plasma prolactin concentration in order to evaluate the efficacy of quinagolide (Norprolac) in patients with prolactinoma resistant to ergot dopamine agonists.

PATIENTS AND METHODS: One hundred seven patients (46 men and 61 women) from 27 centers were included in the statistical analysis. All had previously been treated with a dopamine agonist (bromocriptine). Fifty-five patients had undergone surgery before being administered quinagolide: 17 of the patients had also received radiotherapy (before and after the initiation of treatment with quinagolide in 14 and 3 cases respectively). Quinagolide was given at doses ranging from 75 to 750 microg daily and continued for more than one year for 84 patients.

RESULTS: The prolactin level returned to normal after a mean interval of 9.8 1.6 months (1-48) in 47 of the 107 patients (44%) using a mean dose of quinagolide of 259 32.7 microg/d (75-750). The plasma prolactin concentration had already been normalized using bromocriptine in three patients. The variation in tumor volume was assessed in 82 patients since 8 had no residual tumor post-operatively and 17 had received radiotherapy: at least partial regression of the tumor was noted in 25 (30.8%), including 16 (19.5%) with a more than 50% decrease in the remaining tumor. The mean time taken to observe the anti-tumoral effect was 16.8 3.1 months (3-78) using a mean dose of quinagolide of 255.4 37.8 microg/d d (75-750). The following predictive indicators were identified concerning the efficacy of quinagolide: a pre-quinagolide prolactin level of<300 ng/ml in the group of patients whose plasma prolactin concentration was normalized, and a mean decrease in prolactin of 619 ng/ml in the group of patients showing a reduction in tumor volume treated with quinagolide for 3 months. Side effects (nausea, vomiting, hypotension) were generally mild and were observed in 51 patients (47.6%). Only 11 (10.2%) of patients had to discontinue treatment because of adverse reactions.

CONCLUSION: An anti-tumoral effect was noted in 30.8% of patients and occurred within an interval of less than 2 years in 80% of cases at a dose of 300 microg/d. Normalization of the plasma prolactin concentration was obtained in 44% of cases and occurred in less than one year in 80% of patients at a dose of 300 microg/d. Quinagolide is a useful drug and from now on should be prescribed as first-line treatment for patients presenting with bromocriptine-resistant prolactinoma.