Somatotroph tumor progression during pegvisomant therapy: a clinical and molecular study.
BACKGROUND
There is concern that pegvisomant could be associated with a higher risk of tumor growth. The rate and possible determinants of this tumor growth are unknown.


OBJECTIVE
The objective of the study was to investigate the clinical, immunohistological, and molecular factors conditioning tumor growth in patients taking pegvisomant.


METHODS
This was a cross-sectional study performed from 2004 to 2010 in four university hospitals in Spain.


METHODS
Seventy-five acromegalic patients with active disease resistant to somatostatin analogs treated with pegvisomant were followed up for a mean of 29 ± 20 months.


METHODS
Magnetic resonance images before initiation of pegvisomant, at 6 months, and then yearly were examined in all patients. Immunohistological and molecular studies were performed in tumors that grew.


RESULTS
A significant increase in tumor size was observed in five patients (6.7%). Absence of previous irradiation (P = 0.014) and shorter duration of prepegvisomant somatostatin analog therapy (P < 0.001) were associated with an increased risk of tumor growth. A stepwise multivariate linear regression analysis (R(2) = 0.334, P < 0.001) identified the duration of somatostatin analog therapy prior to pegvisomant (beta = -4.509, P = 0.014) as the only significant predictor of tumor growth. In those tumors that grew, GH expression and insulin receptor expression were higher (P = 0.033 in both cases) than in the control group.


CONCLUSIONS
No previous radiotherapy, shorter duration of prepegvisomant somatostatin analog therapy, and higher tumor expression of GH and insulin receptor could be risk factors for tumor growth during pegvisomant therapy.
Endocrinology Division, Hospital Universitario de la Princesa, Diego de Leon 62, 28006, Madrid, Spain. mmarazuela.hlpr@salud.madrid.org
M
M
Marazuela
A E
AE
Paniagua
M D
MD
Gahete
T
T
Lucas
C
C
Alvarez-Escolá
R
R
Manzanares
J
J
Cameselle-Teijeiro
M
M
Luque-Ramirez
R M
RM
Luque
E
E
Fernandez-Rodriguez
J P
JP
Castaño
I
I
Bernabeu
D000172:Acromegaly / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology; D000236:Adenoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D010902:Pituitary Gland / Q000473:pathology / Q000601:surgery; D011859:Radiography; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D055815:Young Adult
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; C406545:pegvisomant