Dissecting the in vitro efficacy of octreotide and cabergoline in GH- and GH/PRL-secreting pituitary tumors
F. Gatto*a (Dr), RA. Feeldersb (Dr), P. Van Koetsveldb (Dr), F. Doganb (Dr), SJ. Neggersb (Dr), AJ. Van Der Lelijb (Prof), J. Amarùc (Dr), D. Feronec (Prof), LJ. Hoflandd (Prof)
a IRCCS Ospedale Policlinico San Martino, Genoa, ITALY ; b Erasmus Medical Center, Rotterdam, NETHERLANDS ; c University of Genoa, Genoa, ITALY ; d Eramus Medical Center, Rotterdam, NETHERLANDS
Context. Cabergoline (CAB) is an off-label medical therapy for acromegaly, overshadowed by first-generation somatostatin receptor ligands, e.g. octreotide (OCT).
Objective. Head-to-head comparison between OCT and CAB in inhibiting growth hormone (GH) secretion in primary cultures of GH- and GH/PRL-secreting tumors. To investigate the role of somatostatin (SST) and dopamine type 2 (D2R) receptor expression.
Design. To evaluate the antisecretory effect of OCT and CAB, together with receptor mRNA expression, in 23 tumor cultures.
Setting and Patients. Acromegaly patients referred to the Erasmus Medical Center (Rotterdam, The Netherlands).
Interventions. 72-hour OCT and CAB treatment (10 nM).
Main Outcome Measures. GH (and PRL) concentrations in cell culture media.
Results. OCT showed a trend towards a higher efficacy compared with CAB (GH decrease -39.5% vs. -32.5%, p=0.079). The two drugs were superimposable in GH/PRL co-secreting tumors (-42.1% vs. -44.8%), where SST1 and D2R had a higher expression compared to the pure GH-secreting ones (p=0.020 and p=0.026, respectively). OCT was more potent than CAB in 8/23 cultures, while CAB was more effective than OCT in 3/23 (CAB+ group). In CAB+ tumors, SST1 expression was higher compared to the other groups (p=0.034). At ROC curve analysis, SST1 and D2R discriminated between GH and GH/PRL co-secretion (AUC 0.856, p=0.013; AUC 0.822, p=0.024; respectively). SST1 was the best predictor of CAB response (≥50% GH reduction, AUC 0.913, p=0.006; 80% sensibility, 94% specificity).
Conclusions. OCT is 5-10% more effective than CAB in vitro. SST1 mRNA expression can represent a reliable marker of GH/PRL co-secreting tumors showing a preferential response to CAB treatment.
The author has declared no conflict of interest.