Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: results from a randomized controlled trial

J Hepatol. 2013 Jul;59(1):153-9. doi: 10.1016/j.jhep.2013.03.004. Epub 2013 Mar 14.

Abstract

Background & aims: Polycystic liver disease (PLD) is associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PCLD). The resulting hepatomegaly compromises quality of life. Somatostatin analogues reduce PLD volume by approximately 5% when given for 6-12 months. A pilot trial in 16 ADPKD patients demonstrated that sirolimus, an mTOR inhibitor, reduced PLD volume by 26%. The aim of this study was to assess the PLD volume reducing effect of everolimus and octreotide relative to octreotide monotherapy.

Methods: We designed a randomized controlled trial that compared 48 weeks of everolimus 2.5 mg daily, combined with octreotide 40 mg intramuscularly every 4 weeks, to octreotide monotherapy. We included PCLD and ADPKD patients. Exclusion criteria were MDRD-GFR <60 ml/min/1.73 m(2) and liver volume <2500 ml. Primary outcome was change in liver volume measured with CT-volumetry.

Results: We randomized 44 PLD patients (29 PCLD, 15 ADPKD, 89% female) to treatment with octreotide (n=23) or octreotide-everolimus (n=21). Liver volume decreased by 3.5% (p<0.01) in the monotherapy arm, compared to 3.8% with combination therapy (p<0.01). The difference between treatment arms was not significant (p=0.73).

Conclusions: Adding everolimus to octreotide in PLD does not increase the liver volume reducing effect of octreotide.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cysts / drug therapy*
  • Cysts / pathology
  • Delayed-Action Preparations
  • Drug Therapy, Combination
  • Everolimus
  • Female
  • Humans
  • Kidney / drug effects
  • Kidney / pathology
  • Liver / drug effects
  • Liver / pathology
  • Liver Diseases / drug therapy*
  • Liver Diseases / pathology
  • Male
  • Middle Aged
  • Octreotide / administration & dosage*
  • Organ Size / drug effects
  • Polycystic Kidney, Autosomal Dominant / drug therapy
  • Polycystic Kidney, Autosomal Dominant / pathology
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Everolimus
  • Octreotide
  • Sirolimus

Supplementary concepts

  • Polycystic liver disease