Somatostatin Analog Halves Pancreatic Resection Risk

A new drug that decreases pancreatic exocrine secretions could halve the risk of postoperative pancreatic fistula, according to a new study.

Researchers at Memorial Sloan-Kettering Cancer Center (New York, NY, USA) conducted a randomized, double-blind trial of the use of perioperative subcutaneous pasireotide in patients undergoing either pancreaticoduodenectomy or distal pancreatectomy. The 300 patients were randomly assigned to receive 900 μg of subcutaneous pasireotide (152 patients) or placebo (148 patients) twice daily, beginning preoperatively on the morning of the operation and continuing for 7 days. The primary end point was the development of pancreatic fistula, leak, or abscess of grade 3 or higher that required drainage.

The results showed that the primary end point occurred in 45 of the 300 patients (15%), but was significantly lower among patients who received pasireotide (9%) than among patients who received placebo (21%). The results were consistent in patients who underwent pancreaticoduodenectomy and those who underwent distal pancreatectomy; results were also consistent irrespective of the presence or absence of a dilated pancreatic duct. The study was published on May 22, 2014, in the New England Journal of Medicine (NEJM).

“Fewer than one patient in 10 treated with pasireotide had a grade 3 or higher postoperative pancreatic fistula, leak, or abscess. In contrast, more than one patient in five given a saline placebo had such a complication,” concluded lead author Peter Allen, MD, and colleagues. “The majority of the events represented expected postoperative abnormalities in the results of serum chemical analyses. Not only were many fistulas and leaks prevented, but when they did occur, they were less clinically relevant.”

Pancreatic secretion is composed of two products critical to proper digestion: bicarbonate and a battery of digestive enzymes that collectively have the capacity to reduce digestible macromolecules into forms that are capable of being absorbed. These include three major groups of enzymes: proteases (trypsin and chymotrypsin); lipase, which performs the hydrolysis of triglycerides; and amylase, which hydrolyses starch to maltose. The somatostatin analog Pasireotide, an orphan drug originally developed by Novartis (Basel, Switzerland) for the treatment of Cushing's disease, was found to have a 40-fold increased affinity to somatostatin receptor 5 than other analogs.

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Memorial Sloan-Kettering Cancer Center