Express Communication - 03014
1208
Regression of Hepatocellular Cancer in a Patient Treated with Arginine Deiminase
Steven A Curley, John S Bomalaski 1, C Mark Ensor 1, Frederick W Holtsberg 1, Mike A Clark 1
University of Texas, MD Anderson Cancer Center, Houston, Texas and 1University of Kentucky
Department of Biology and Phoenix Pharmacologics, Inc., Lexington, Kentucky, USA Corresponding Author: Steven A. Curley, MD, FACS, Department of Surgical Oncology
M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard
Box 444, Houston, Texas 77030-4095, USA
Tel: +1 713 794 4957, Fax: +1 713 745 5235, E-mail: scurley@https://www.doczj.com/doc/666897908.html,
SUMMARY
We report the first pharmacokinetic and clinical response data from a patient with unresectable hep-atocellular cancer treated with a new drug, ADI-PEG 20,000 mw (arginine deiminase-polyethylene glycol 20,000 molecular weight).
A single patient with idiopathic cirrhosis and unre-sectable hepatocellular cancer was treated with esca-lating dosages of ADI-PEG 20,000 mw . Human hepato-cellular cancer has been found to be arginine-depen-dent for growth because of loss of expression or arginosuccinate synthetase, the rate-limiting enzyme in the conversion of citrulline to arginine. Thus, an arginine-degrading enzyme like ADI-PEG 20,000 mw should produce cell death in hepatocellular cancer cells without significantly affecting normal cells.
There was a dose-dependent reduction of plasma arginine levels after weekly intramuscular adminis-tration of ADI-PEG 20,000 mw . Successive treatment cycles at the optimal biologic dose of 160 IU/m2 led to reduction in tumor size and serum alpha-fetoprotein levels. Sufficient tumor cytoreduction was achieved with ADI-PEG 20,000 mw treatment to permit surgical treatment. The patient developed no toxicities or side effects related to ADI-PEG 20,000 mw treatment.
The results in a single patient with unresectable hepatocellular cancer treated with ADI-PEG 20,000 mw suggests this may be a promising, low-toxicity treat-ment. Full-scale clinical trials have been initiated.
KEY WORDS: Hepatocellular cancer; Arginine deiminase ABBREVIATIONS: Hepatocellular Cancer (HCC);Arginine Deiminase-Polyethylene Glycol 20,000molecular weight (ADI-SS PEG 20,000mw ); Arginosucci-nate Synthetase (ASS); Computed Tomography (CT);Alpha Fetoprotein (AFP)
HCC Treated by Arginine Deiminase Hepato-Gastroenterology 50 (2003) 1209
1210Hepato-Gastroenterology 50 (2003)SA Curley, JS Bomalaski, CM Ensor, et al