The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas
Authors: Di Sarno Antonella , Landi Maria Luisa , Marzullo Paolo , Di Somma Carolina , Pivonello Rosario , Cerbone Gaetana , Lombardi Gaetano , Colao Annamaria 
Published: March 2003

OBJECTIVE

To compare effectiveness and tolerability of quinagolide (CV 205–502) and cabergoline (CAB) treatments in 39 patients with prolactinoma.

STUDY DESIGN

All 39 patients were treated first with quinagolide for 12 months and then with cabergoline for 12 months. A wash‐out period was performed in all patients after 12 months of both treatments in order to evaluate recurrence of hyperprolactinaemia.

PATIENTS

Twenty‐three patients with microprolactinoma (basal serum PRL levels 1620–18750 mU/l) and 16 patients with macroprolactinoma (basal serum PRL levels 4110–111000 mU/l), previously shown to be intolerant of bromocriptine. All patients had gonadal failure and 11 patients with macroprolactinoma had visual field defects. Five patients with macro‐ and one with microprolactinoma had previously undergone surgery.

STUDY PROTOCOL

The starting doses of quinagolide and CAB were 0.075 mg/day and 0.5 mg/week, respectively, subsequently increased up to 0.6 mg once daily and 1.5 mg twice weekly, respectively. Serum PRL levels were measured monthly for the first 3 months and then quarterly for 12 months. PRL levels were assayed weekly for the first month and then monthly during the wash‐out period. Tumour shrinkage was evaluated by serial magnetic resonance imaging (MRI) studies of the hypothalamus–pituitary region at study entry and after 6 and 12 months of both treatments in micro‐ and macroprolactinomas.

RESULTS

After 12 months of quinagolide treatment, serum PRL levels normalized in all 23 patients with microprolactinoma (100%) and in 14 out of 16 with macroprolactinoma (87.5%). A tumour volume reduction of greater than 80% was documented by MRI studies in five of 23 (21.7%) patients with microprolactinoma and in four of 16 (25%) with macroprolactinoma. All patients had recurrence of hyperprolactinaemia after 15–60 days withdrawal of quinagolide treatment. However, before starting CAB treatment basal PRL levels were significantly lower than before quinagolide treatment both in microprolactinomas (4667.4 ± 714.7 vs. 2636.1 ± 262.3 mU/l, P = 0.006) and in macroprolactinomas (24853.1 ± 7566.7 vs. 3576.6 ± 413.0 mU/l, P = 0.013). After 12 months of CAB treatment, serum PRL levels normalized in 22 out of 23 patients with microprolactinoma (95.6%) and in 14 out of 16 with macroprolactinoma (87.5%). No difference in PRL nadir was found after quinagolide and CAB treatments both in micro 174.6 ± 30.6 vs. 169.8 ± 37.9 mU/l, P = 0.5) and in macroprolactinomas (277.5 ± 68.4 vs. 341.8 ± 95.2 mU/l, P = 0.6). A tumour volume reduction of greater than 80% was documented by MRI studies in seven other patients with microprolactinoma (30.4%) and in five other patients with macroprolactinoma (31.2%). After CAB treatment, further tumour shrinkage ranging 4–40% and 2–70% was observed in 12 micro‐ and seven macroprolactinomas, respectively. The percentage of tumour shrinkage after CAB was significantly higher than that observed after quinagolide in microprolactinomas (48.6 ± 9.5 vs. 26.7 ± 4.5%, P = 0.046) but not in macroprolactinomas (47.0 ± 10.6 vs. 26.8 ± 8.4%, P = 0.2). The withdrawal from CAB treatment, induced an increase in serum PRL levels in all macroprolactinomas between 15 and 30 days, in 15 out of 23 microprolactinoma after 30 days, and in four patients after 2–4 months. In the remaining four patients serum PRL levels remained normal after 12 months of CAB withdrawal. Both compounds were tolerated satisfactorily by all patients. In the first week of quinagolide treatment, 12 patients reported nausea and postural hypotension, which spontaneously disappeared during the second‐third week of treatment. None of the 39 patients reported side‐effects during CAB treatment.

CONCLUSIONS

Both quinagolide and CAB treatments, induced the normalization of serum PRL levels in the great majority of patients with prolactinoma. Tumour shrinkage was recorded in 22–25% of patients after quinagolide and in 30–31% after CAB treatment. However, CAB induced notable tumour shrinkage even in patients who had partial tumour reduction after quinagolide. CAB treatment was tolerated better than quinagolide treatment in 12 out of 39 patients (30.7%). On this basis, both compounds can be used as first line treatment in prolactinomas, while CAB is preferable in patients poorly tolerant to other dopamine agonists. Finally, the long‐lasting hypoprolactinemic effect of CAB allowed an intermittent treatment schedule in eight out of 23 patients with microprolactinomas with a better cost:effectiveness ratio.