Regression of hepatocellular cancer in a patient treated with arginine deiminase.
We report the first pharmacokinetic and clinical response data from a patient with unresectable hepatocellular cancer treated with a new drug, ADI PEG20,000 mw (arginine deiminase-polyethylene glycol 20,000 molecular weight). A single patient with idiopathic cirrhosis and unresectable hepatocellular cancer was treated with escalating dosages of ADI-PEG20,000 mw. Human hepatocellular cancer has been found to be arginine-dependent 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-PEG20,000 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 administration of ADI-PEG20,000 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-PEG20,000 mw treatment to permit surgical treatment. The patient developed no toxicities or side effects related to ADI-PEG20,000 mw treatment. The results in a single patient with unresectable hepatocellular cancer treated with ADI-PEG20,000 mw suggests this may be a promising, low-toxicity treatment. Full-scale clinical trials have been initiated.
Curley
Steven A
SA
Department of Surgical Oncology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Box 444, Houston, Texas 77030-4095, USA. scurley@mdanderson.org
Bomalaski
John S
JS
Ensor
C Mark
CM
Holtsberg
Frederick W
FW
Clark
Mike A
MA
D001120:Arginine / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000008:administration & dosage / Q000627:therapeutic use*; D007273:Injections, Intramuscular; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008875:Middle Aged; D011092:Polyethylene Glycols
D011092:Polyethylene Glycols; D001120:Arginine; D006867:Hydrolases; C019723:arginine deiminase