Protection of normal tissues from radiation and cytotoxic therapy: the development of amifostine.
Much effort is being made to reduce the iatrogenic toxicity of antineoplastic treatments in order to improve the quality of life of cancer patients. Cytoprotection of healthy tissue by thiol group donors is one of the most promising lines of research. Amifostine is the most extensively studied drug in the category. We reviewed the extensive medical literature on amifostine. The protective effect of amifostine has been demonstrated for cisplatin-induced toxicity in lung and ovarian cancer, with particular regard to nephrotoxicity, neurotoxicity and neutropenia. No protective effect has been seen for tumor cells owing to a selective action of amifostine on healthy tissues. A frequent side effect of amifostine is a transient decreases in blood pressure; it is usually asymptomatic if an easily handled premedication is given. Cytoprotection by amifostine is also well known for alkylating drugs and radiation therapy, whereas it is still the object of study for new drugs, especially taxanes. The present work also includes a cost-benefit analysis and a prospective view on the most promising research lines.
Castiglione
F
F
Service of Medical Oncology, Civic Hospital, Alba, Italy. castiglione@dada.it
Dalla Mola
A
A
Porcile
G
G
D004999:Amifostine / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D011837:Radiation-Protective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D011878:Radiotherapy / Q000009:adverse effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D004999:Amifostine