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

Eur J Endocrinol. 2009 Apr;160(4):529-33. doi: 10.1530/EJE-08-0843. Epub 2009 Jan 13.

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 (n=63) 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; p=0.03) 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.

MeSH terms

  • Acromegaly / drug therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetes Complications / physiopathology
  • Drug Therapy, Combination
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / therapeutic use
  • Humans
  • Liver Function Tests
  • Male
  • Middle Aged
  • Octreotide / therapeutic use
  • Peptides, Cyclic / therapeutic use
  • Receptors, Somatotropin / antagonists & inhibitors*
  • Somatostatin / adverse effects
  • Somatostatin / analogs & derivatives*
  • Somatostatin / therapeutic use*
  • Young Adult

Substances

  • Peptides, Cyclic
  • Receptors, Somatotropin
  • lanreotide
  • Human Growth Hormone
  • Somatostatin
  • pegvisomant
  • Octreotide