The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas.
OBJECTIVE
To compare effectiveness and tolerability of quinagolide (CV 205-502) and cabergoline (CAB) treatments in 39 patients with prolactinoma.


METHODS
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.


METHODS
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.


METHODS
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
Department of Molecular and Clinical Endocrinology and Oncology, 'Federico II' University of Naples, Italy.
A
A
Di Sarno
M L
ML
Landi
P
P
Marzullo
C
C
Di Somma
R
R
Pivonello
G
G
Cerbone
G
G
Lombardi
A
A
Colao
D000328:Adult; D000634:Aminoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000077465:Cabergoline; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D004873:Ergolines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D016896:Treatment Outcome
D000634:Aminoquinolines; D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; C046650:quinagolide; D011388:Prolactin; D000077465:Cabergoline