Drug & Device Development

Octreotide shrinks polycystic livers and kidneys

Last Updated: 2010-04-29 17:00:17 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - Treatment with the somatostatin analog octreotide (Sandostatin LAR, Novartis) can slow or reverse the effects of polycystic kidney and liver disease, a recent pilot study has shown.

"Somatostatin analogs could provide the first viable non-surgical treatment for these diseases," lead author Dr. Marie C. Hogan told Reuters Health by email.

During the one-year trial, octreotide LAR depot reduced liver volume in patients with polycystic liver disease, and it stabilized kidney volume in patients with autosomal dominant polycystic kidney disease, according to Dr. Hogan and her colleagues at the Mayo Clinic in Rochester, Minnesota.

Somatostatin analogs blunt cyst development by inhibiting generation of cyclic AMP in cholangiocytes and in tubular epithelial cells and by suppressing cystogenic growth factors, the researchers say in their April 29th online report in the Journal of the American Society of Nephrology.

"Octreotide is already FDA-approved and used in thousands of patients with acromegaly, metastatic carcinoid tumors, and in people who have chronic diarrhea due to vasoactive intestinal peptide-secreting tumors," Dr. Hogan said.

For their pilot study, they enrolled 42 patients -- 34 with autosomal dominant polycystic kidney disease and 8 with autosomal dominant polycystic liver disease. (Both diseases produce multiple hepatic cysts; all subjects had enlarged livers.) They randomly assigned 28 patients to the octreotide group (40 mg IM every 28 days) and 14 to the placebo group.

Baseline magnetic resonance imaging or computed tomography showed mean liver volumes of 5908 mL in the octreotide group and 5374 mL in the placebo group.

After 12 months, mean liver volume had decreased by 4.95% with octreotide, whereas it had increased by 0.92% with placebo (p = 0.048). Twenty-one patients (75%) in the octreotide group had reduced liver volume.

In 29 patients with polycystic kidney disease, mean baseline kidney volume was 1143 mL in the octreotide group and 803 mL in the placebo group. The mean kidney volume increased by 0.25% with octreotide and by 8.61% with placebo (p = 0.045).

Changes in liver and kidney volumes in response to octreotide treatment were significantly correlated with baseline volumes. The larger the liver or kidney at baseline, the larger the reduction, according to the authors.

Declines in glomerular filtration rate (5.1% with octreotide and 7.2% with placebo) were similar in the two groups.

On a health-related quality of life questionnaire, physical role and bodily pain significantly improved in the octreotide-treated group only.

The most common side effects of octreotide were injection site pain and granulomas, and diarrhea. Moderate alopecia, symptomatic bradycardia requiring an emergency room visit, and steatorrhea and weight loss each developed in one patient. Plasma glucose level increased by 10% over baseline in the octreotide group and by 2% with placebo.

"Further long-term safety and efficacy data will be needed before (somatostatin analogs) can be routinely recommended as a long-term therapy," Dr. Hogan said.

To that end, subjects in the current study are eligible to continue in a 2-year open-label extension.

This study gives hope that "increases in polycystic liver and kidney volume can be attenuated and thereby improve morbidity and mortality" in patients with autosomal dominant polycystic kidney disease, Dr. Robert W. Schrier, from the University of Colorado Denver in Aurora, writes in an editorial.

This study was partially funded by Novartis. Two authors have patents pending for methods of using somatostatin analogs to treat polycystic liver disease.

J Am Soc Nephrol 2010.