Reducing the toxicity of anticancer therapy: new strategies.

Cytoprotective agents offer opportunities to reduce the treatment-related toxicity of anticancer therapy and perhaps to increase the dose and dose intensity of radiation and chemotherapy. One such agent is amifostine, an organic thiophosphate. Amifostine selectively protects normal tissues and provides broad-spectrum protection for a variety of organs while remaining minimally toxic. Clinical studies have demonstrated that amifostine protects against myelotoxicity, nephrotoxicity, neurotoxicity, mucositis and esophagitis in patients treated with alkylating and platinum agents, paclitaxel and radiation therapy. In addition, preclinical studies suggest the possibility of protection against anthracycline-induced cardiotoxicity and radiation- and chemotherapy-induced mutagenicity. Preclinical and clinical studies have not demonstrated any diminution of antitumor efficacy. Amifostine is well tolerated in doses of 740 or 910 mg/m2. The most common side effects requiring treatment are transient hypotension, which responds to intravenous fluids, and nausea and vomiting, effectively treated with 5-HT3 antagonists and dexamethasone.