Drug & Device Development

Pegylated arginine deiminase has potential for unresectable hepatoma

Last Updated: 2010-03-31 18:14:20 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Pegylated arginine deiminase might prolong survival in patients with unresectable hepatocellular carcinoma, phase II trial data suggest.

The investigators point out that depriving hepatocellular carcinoma (HCC) cells of arginine induces apoptosis, and that enzyme deprivation has been effective in other types of cancer.

In their March 29th online paper in the Journal of Clinical Oncology, Dr. Steven A. Curley of the M.D. Anderson Cancer Center in Houston, Texas and colleagues report on 76 patients with inoperable HCC who received arginine deiminase weekly for up to six months, in doses of either 80 or 160 IU/m2.

The overall mean and median survival were 15.8 and 11.4 months, respectively. Mean survival was nonsignificantly longer in the high-dose group (16.1 months) than in the low-dose group (15.4 months). In patients who completed 4 to 6 months of treatment, mean and median survival rose to nearly 20 and 16 months, respectively.

There was one complete and one partial response to the treatment, and 60.5% of patients achieved stable disease.

The therapy was generally well tolerated. There were 220 adverse events, with 19.5% grade 3 or worse. Only 31 events (14.1%) were related to the study drug; the most common of these were transient encephalopathy, skin irritation or discomfort at the injection site, and fever. Two patients had grade 2 delayed hypersensitivity reactions at the injection site and were removed from the study but included in analyses.

"We suspect that a combination of therapies-arginine deprivation, growth inhibition via kinase inhibitors, and possibly cytotoxic chemotherapy-will continue to improve survival due to multiple simultaneous insults on any given malignant cell," the researchers write. "Using multiple agents in parallel, we theorize, would result in improved outcomes compared with serial treatments."

J Clin Oncol 2010.