A Phase I Clinical and Pharmacology Study Using Amifostine as a Radioprotector in Dose-escalated Whole Liver Radiation Therapy

Mary Feng, David E. Smith, Daniel P. Normolle, James A. Knol, Charlie C. Pan, Edgar Ben-Josef, Zheng Lu, Meihua R. Feng, Jun Chen, William Ensminger, Theodore S. Lawrence, Mary Feng, David E. Smith, Daniel P. Normolle, James A. Knol, Charlie C. Pan, Edgar Ben-Josef, Zheng Lu, Meihua R. Feng, Jun Chen, William Ensminger, Theodore S. Lawrence

Index: Int. J. Radiat. Oncol. Biol. Phys. 83(5) , 1441-7, (2012)

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Abstract

Purpose Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy.