Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients.
BACKGROUND
Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood.


METHODS
A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB ≥2.0 mg weekly.


RESULTS
Ninety-two patients (50 F, 42 M) were analyzed. At diagnosis, most had macroprolactinomas (82.6%); males were significantly older than females (P=0.0003) and presented with a more aggressive disease. A genetic basis was identified in 12 patients. Thirty-six patients (39.1%) received only medical therapy, most underwent surgery (60.9%, including multiple interventions in 10.9%), and 14.1% received postoperative radiotherapy. Eight patients developed late CAB resistance (8.7%). The median maximal weekly dose of CAB (CAB(max/w)) was 3.5 mg (2.0-10.5). Despite a higher CAB(max/w) in patients treated with multimodal therapy (P=0.003 vs exclusive pharmacological treatment), a debulking effect of surgery was shown in 14 patients, with a higher rate of PRL control (P=0.006) and a significant reduction in CAB(max/w) (P=0.001) postoperatively. At last follow-up (median 88 months), PRL normalization and tumor disappearance were achieved in 28 and 19.9% of the patients respectively, with no significant sex-related difference observed in CAB(max/w) or disease control. Mortality was 4.8%, with four patients developing aggressive tumors (4.3%) and three a pituitary carcinoma (3.3%).


CONCLUSIONS
CAB-resistant prolactinomas remain a serious concern. Surgical debulking, newer therapeutic strategies, and early diagnosis of genetic forms could help to improve their outcome.
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Belgium.
Laurent
L
Vroonen
Marie-Lise
ML
Jaffrain-Rea
Patrick
P
Petrossians
Gianluca
G
Tamagno
Philippe
P
Chanson
Lucio
L
Vilar
Françoise
F
Borson-Chazot
Luciana A
LA
Naves
Thierry
T
Brue
Blandine
B
Gatta
Brigitte
B
Delemer
Enrica
E
Ciccarelli
Paolo
P
Beck-Peccoz
Philippe
P
Caron
Adrian F
AF
Daly
Albert
A
Beckers
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000077465:Cabergoline; D017024:Chemotherapy, Adjuvant; D002648:Child; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004873:Ergolines / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000209:etiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D015175:Prolactinoma / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012189:Retrospective Studies; D017211:Treatment Failure
D000970:Antineoplastic Agents; D004873:Ergolines; D047908:Intracellular Signaling Peptides and Proteins; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D000077465:Cabergoline