The role of amifostine in the treatment of head and neck cancer with cisplatin-radiotherapy

Although head and neck cancer is not one of the most common cancers, it is a debilitating disease with poor prognosis and considerable post-treatment normal tissue toxicity. The unremitting search to increase the therapeutic ratio between tumour control and late normal tissue injury led to the adoption of altered fractionation schedules. While the increase in acute toxicity can be managed with appropriate medical support, damage produced to late responding tissues is usually irreversible, therefore clinically unacceptable. By altering the conventionally fractionated radiotherapy both loco-regional control and overall survival are increased. Moreover, phase III randomized trials indicated that the combined administration of cisplatin and radiotherapy further improves treatment outcome. Although the uptake of cisplatin in normal cells is not amplified by the combined modality treatment, cisplatin, by itself is a highly cytotoxic agent. Therefore, the need for normal tissue protection has arisen. Amifostine is a selective, radio-protective drug used in both radiotherapy and chemotherapy to reduce normal tissue toxicity. This paper provides an overview of clinical trials employing cisplatin-radiotherapy treatment for advanced head and neck cancer with specific focus on normal tissue toxicity. The emerging role of radioprotectors and furthermore, the effectiveness of amifostine in combined cisplatin-radiotherapy trials are presented.