Safety and efficacy evaluation in patients from the German acrostudy

I. Schreiber; K. Forssmann; M. Buchfelder; M. Droste; K. Mann; B. Saller; C. J. Strasburger

doi:10.1055/s-2006-932933

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Safety and efficacy evaluation in patients from the German acrostudy

I Schreiber ¹, K Forssmann ¹, M Buchfelder ², M Droste ³, K Mann ⁴, B Saller ⁵, CJ Strasburger ⁶

¹Pfizer Pharma GmbH, Karlsruhe, Germany
²Universität Erlangen/Nürnberg, Erlangen, Germany
³Praxis, Oldenburg, Germany
⁴Universitätsklinikum Essen, Essen, Germany
⁵EndoScience Endokrinologie Service GmbH, München, Germany
⁶Charite Campus Mitte, Berlin, Germany

Abstract

The approval of pegvisomant (Somavert) has augmented the therapeutic options in acromegaly. Between Jan 04 and Jul 05, 184 pts were enrolled in the German Acrostudy. Pts age was 49.2±13.5yrs. 91% pts underwent pituitary surgery, 45% received radiation therapy, and previous medical therapy included dopamine agonists (56%), octreotide (90%) and/or lanreotide (10%). Efficacy analysis was performed in 134 pts with a follow-up after 6 months, in 99 pts after 12 months and in 22 pts after 2 years. Mean duration of pegvisomant therapy was 42.2±30.0 wks. During pegvisomant therapy with dose titration not escalated to normalize IGF-I in some, IGF-I was normalized in 65.4% at 6 months with a mean dose of 16.8mg/d and a median dose of 15.0mg/d. IGF-I levels were normalized in 90.2% of pts treated for at least 2 years. Elevated liver function tests (LFT) >3 times above normal occurred in 9 pts receiving octreotide before. In 6/9 pts, LFTs spontaneously normalized during continued treatment, in the other 3 pts (1.6%), levels normalized after treatment discontinuation. With the exception of one patient with transient LFT elevation obviously due to a singular alcohol excess, ALT was the enzyme most prominently elevated. Progression of remnant pituitary adenoma was reported in a total of 9 pts. 7 cases were re-evaluated by a independent neurosurgeon. In 3 pts tumor progression could not be verified at re-evaluation. In 2 pts, the tumor had continuously grown already before pegvisomant therapy, while on somatostatin analogues. In one case, a slight and clinically non-significant growth was seen during pegvisomant therapy and one pt showed a tumor growth due to rebound from somatostatin-induced shrinkage. Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials, and can effectively reduce IGF-I in pts refractory to conventional therapy. In conclusion, the German Acrostudy is at present the globally larges database on patients treated with pegvisomant. It provides important information on safety and efficacy on these treatment.