Amifostine and combined-modality therapeutic approaches

Abstract

Recent interest has focused on the use of amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) as a possible multiorgan combined-modality protector. Amifostine has been shown to selectively protect normal tissues from the cytotoxic and mutagenic effects of alkylating and platinum-based chemotherapy and ionizing radiation. There are a number of approaches to ameliorating therapy-related toxicities, including the use of individual agents that target specific toxicities. However, amifostine is unique in that it possesses a broad range of tissue-protective effects. Amifostine has been studied in clinical trials comprising patients with lung cancer, head and neck cancer, and cancer of the cervix. Results of these trials show that amifostine can be safely administered to patients receiving chemotherapy and radiation therapy. These trials also demonstrate that amifostine has the potential to be a broad-spectrum cytoprotectant of normal tissues from the toxicities of radiation, as well as certain forms of chemotherapy. The selective cytoprotective effects of amifostine allow for the use of higher doses of cytotoxic therapy. Theoretically, this could improve therapeutic outcome in patients with cancer.