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Somatotroph Tumor Progression during Pegvisomant Therapy: A Clinical and Molecular Study

2010; Oxford University Press; Volume: 96; Issue: 2 Linguagem: Inglês

10.1210/jc.2010-1742

1945-7197

Mónica Marazuela, Amalia-Elisa Paniagua, Manuel D. Gahete, T. Lucas, Cristina Álvarez‐Escolá, Rafael González Manzanares, José Cameselle‐Teijeiro, Manuel Luque‐Ramírez, Raúl M. Luque, Emilio Fernández Rodríguez, Justo P. Castaño, Ignacio Bernabéu,

Neuroendocrine Tumor Research Advances

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.The objective of the study was to investigate the clinical, immunohistological, and molecular factors conditioning tumor growth in patients taking pegvisomant.This was a cross-sectional study performed from 2004 to 2010 in four university hospitals in Spain.Seventy-five acromegalic patients with active disease resistant to somatostatin analogs treated with pegvisomant were followed up for a mean of 29 ± 20 months.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.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.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.