Drug & Device Development

Reduced lanreotide dose still effective in polycystic liver disease

Last Updated: 2013-07-08 13:58:51 -0400 (Reuters Health)

By Will Boggs MD

NEW YORK (Reuters Health) - A 90-mg dose of lanreotide has fewer side effects than a 120-mg dose and still reduces liver volume in polycystic liver disease, according to results from the LOCKCYST I and II trials.

"In symptomatic patients we would favor to start the highest dose of lanreotide (120 mg), since this has the greatest (chances) to ease symptoms," Dr. Frederik Temmerman from University Hospitals KULeuven, Leuven, Belgium told Reuters Health. "In case of intolerance...a dose reduction to lanreotide 90 mg is meaningful, since this has still a beneficial effect compared to placebo."

Polycystic liver disease (PCLD) may accompany autosomal dominant polycystic kidney disease, which affects one in 800-1000 people, or occur as a rare isolated disorder (affecting one in 100,000 people).

Lanreotide, often used to treat acromegaly, is a somatostatin analog that inhibits Insulin-like growth factor-1 and growth hormone. It's known to reduce liver volume and improve quality of life in PCLD, but the optimal dose has not been investigated before.

In a study partly funded by Ipsen Pharma, which makes lanreotide, Dr. Temmerman and colleagues assessed the safety and efficacy of the 90- and 120-mg doses for PCLD by pooling data from the LOCKCYST I and LOCKCYST II trials.

Of the 132 patients included in the study, 26 received placebo, 51 received 120 mg lanreotide, and 55 received 90 mg lanreotide, according to a report online June 25 in Alimentary Pharmacology & Therapeutics.

After six months of treatment, liver volume increased by 36 mL in the placebo group and decreased by 82 mL and 123 mL in the 90-mg and 120-mg lanreotide groups, respectively (p=0.002 for trend).

The difference in the reduction of liver volume between lanreotide 90 mg and lanreotide 120 mg was not statistically significant.

Reductions in liver volume of at least 120 mL were significantly related to relief of symptoms. Similar numbers of patients in the 90-mg group (45%) and 120-mg group (41%) reported fewer symptoms after treatment (p=0.09).

"A reduction of at least 120 mL after six months has a positive predictive value of 64% in easing symptoms after six months," Dr. Temmerman said. "In future trials, a reduction >100-120 mL needs to be the aim of therapy."

Patients treated with 120 mg lanreotide also experienced significant reductions in kidney volume (compared with placebo). Glomerular filtration rates decreased to a greater extent in placebo patients (-2 mL/min/1.73 m2) and 90-mg lanreotide patients (-2.8 mL/min/1.73 m2) than in the 120-mg lanreotide group (-0.24 mL/min/1.73 m2), but the differences between the groups were not statistically significant.

Treatment with 120 mg lanreotide was associated with more serious adverse events (eight patients, 16%) than was treatment with 90 mg lanreotide (four patients, 7%), but the differences were not statistically significant. With the exception of flatulence, all side effects occurred numerically more often in the 120-mg lanreotide group.

"Both lanreotide doses (90 mg and 120 mg) have their influence on the natural history of polycystic liver disease," Dr. Temmerman concluded. "Lanreotide 90 mg is also able to induce a reduction in liver volume, and the lower dose has less pronounced side effects compared to the higher dose (less steatorrhea)."

"It is possible," his group wrote in their paper, "that there is no difference between both doses in the effect on liver volume or that the difference is rather small and not detectable with the actual sample sizes due to lack of statistical power."

SOURCE: http://bit.ly/14vrvBU

Aliment Pharmacol Ther 2013.