Long-term treatment of acromegalic patients resistant to somatostatin analogues with the GH receptor antagonist pegvisomant: its efficacy in relation to gender and previous radiotherapy.
BACKGROUND
Pegvisomant is an effective treatment for somatostatin analogue-resistant acromegaly, but the determinants defining the response to this treatment are largely unknown.


OBJECTIVE
To investigate the efficacy of pegvisomant treatment in resistant acromegalic patients (e.g. serum IGF1 at least 1.25 x upper normal limit) in a clinical setting and the factors conditioning this response.


METHODS
A retrospective cross-sectional study performed in six Spanish University hospitals from 2004 to 2007. Patients Forty-four acromegalic patients (61.4% female, mean age: 49+/-14), 95% of whom had undergone pituitary surgery and 61% having received pituitary radiotherapy. The mean follow-up was 22.7+/-11.2 months. Main outcome measures IGF1 levels reflected treatment efficacy, and the influence of gender, age, weight, previous radiotherapy and duration of treatment was assessed.


RESULTS
IGF1 normalisation was achieved in 84% of the patients. Male gender (P<0.05), previous irradiation (P<0.05) and the treatment duration (r=0.364, P<0.02) were associated with a better response to pegvisomant therapy. There was a significant decrease in HbA1c (P<0.001) and in the mean insulin dose (P<0.01) in acromegalic diabetic patients. Although 25% of patients experienced mild adverse events, pegvisomant was only withdrawn in four patients due to side effects (two cases of tumour growth, one liver dysfunction and one headache).


CONCLUSIONS
Long-term pegvisomant is a very effective therapy in resistant acromegaly. Male gender and prior radiotherapy influence the therapeutic response rate.
Marazuela
Mónica
M
Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Spain. mmarazuela.hlpr@madrid.salud.org
Lucas
Tomás
T
Alvarez-Escolá
Cristina
C
Puig-Domingo
Manel
M
de la Torre
Nuria Garcia
NG
de Miguel-Novoa
Paz
P
Duran-Hervada
Alejandra
A
Manzanares
Rafael
R
Luque-Ramírez
Manuel
M
Halperin
Irene
I
Casanueva
Felipe F
FF
Bernabeu
Ignacio
I
D000172:Acromegaly / Q000188:drug therapy* / Q000532:radiotherapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D048909:Diabetes Complications / Q000188:drug therapy; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012727:Sex Characteristics; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D055815:Young Adult
D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant