Radiation-induced toxicities: the role of radioprotectants

Ionizing radiation has been used to treat many malignancies since the turn of the century. Modern radiotherapeutic techniques have led to increased cure rates and improved local regional control, but the potentially severe and debilitating adverse effects of radiation therapy have not been fully eliminated. Managing radiation-induced toxicities often focuses on treating the symptoms as they manifest. However, preventing these complications is clearly more desirable. Radiation-induced toxicities may be ameliorated in several ways. Dose fractionation was one of the earliest methods recognized to decrease radiation-induced toxicities. Another early method was the use of physical shielding to reduce the area of exposure. Pharmacologic approaches to improving the therapeutic index of radiotherapy fall under two categories: radiosensitizers or radioprotectants. Radiosensitizers are compounds that enhance the sensitivity of tumors to the effects of radiation, but not normal tissue. Radioprotectants such as amifostine function by reducing the effects of radiation on normal cells while maintaining tumor sensitivity. Clinical trials have demonstrated that amifostine can reduce both acute and late radiation-induced toxicities. The development of amifostine has thus resulted in greater tumor control without sacrificing patient well-being. Further investigations are necessary to ensure that patients receive the optimum therapeutic benefit.