Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients

Abstract

Background: We previously reported on the efficacy, safety, and quality of life (QoL) of long-acting somatostatin analogs (SSA) and (twice) weekly pegvisomant (PEG-V) in acromegaly and improvement after the addition of PEG-V to long-acting SSA. Objective: To assess the long-term safety in a larger group of acromegalic patients over a larger period of time: 29.2 (1.2-57.4) months (mean (range)). Design: Pegvisomant was added to SSA monotherapy in 86 subjects (37 females), to normalize serum IGF1 concentrations (nZ63) or to increase the QoL. The median dosage was 60.0 (20-200) mg weekly. Results: After a mean treatment period of 29.2 months, 23 patients showed dose-independent PEG-V related transient liver enzyme elevations (TLEE). TLEE occurred only once during the continuation of combination therapy, but discontinuation and re-challenge induced a second episode of TLEE. Ten of these patients with TLEE also suffered from diabetes mellitus (DM). In our present series, DM had a 2.28 odds ratio (CI 1.16-9.22; pZ0.03) higher risk for developing TLEE. During the combined therapy, a clinical significant decrease in tumor size by more than 20% was observed in 14 patients. Two of these patients were previously treated by pituitary surgery, 1 with additional radiotherapy and all other patients received primary medical treatment. Conclusion: Long-term combined treatment with SSA and twice weekly PEG-V up to more than 4 years seems to be safe. Patients with both acromegaly and DM have a 2.28 higher risk of developing TLEE. Clinical significant tumor shrinkage was observed in 14 patients during combined treatment.

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

“…PEG is usually administered as daily s.c. injections; weekly or twice-weekly dosing (median doses 60 mg weekly) is another effective option though not currently in use (Neggers et al 2009). It is generally well tolerated, with adverse reactions in !10% of cases (increases in liver enzymes, injection site reactions, and headache; Schreiber et al 2007).…”

“…It is generally well tolerated, with adverse reactions in !10% of cases (increases in liver enzymes, injection site reactions, and headache; Schreiber et al 2007). With combined SSA-PEG treatment for 4.5 years, transaminase levels increased in 27% of cases (Neggers et al 2009). However, with careful, continuous monitoring, the combined PEG-SSA treatment is widely used and highly effective: PEG added to patients uncontrolled by maximal doses of SSA normalize IGF1 in 95% of cases (Neggers et al 2009).…”

Cabergoline treatment in acromegaly: cons

“…There is no study specifically addressing the outcome of tumor volume using a combination therapy. Although a percentage of patients' cases can be controlled with the addition of CAB to SSA therapy, the addition of pegvisomant, a GH receptor antagonist, has also been reported in the literature, with much higher efficacy [29][30][31]. The association of other drugs with PEG in patients resistant to the treatment with the former is based in the knowledge that the shrinkage effects of SSA or CAB may occur in some patients independent of the tight biochemical control, probably depending on the SSTR expression profile of the tumor for the SSA therapy [32,33].…”

The Results Of Pegvisomant Treatment In Acromegaly And Review of The Literature

“…Pegvisomant monoterapsisi tümör büyümesini engellemede yetersizdir. Seksen altı hastanın alındığı bir çalışmada pegvisomant ve uzun etkili somatostatin kombinasyon terapisi ile 14 hastada tümör boyutlarında istatistiksel anlamlı oranda (≥%20) küçülme sağlandığı gösterilmiş ve hiçbir hastada tümör volümünde artış saptanmamıştır [25]. Kombinasyon tedavisi uzun etkili somatostatin analoglarında olduğu gibi tümör volümünde küçülme sağlarken pegvisomant monoterapisinde olduğu gibi etkinliği de yüksek bir tedavi modalitesidir.…”