Amifostine and Hematologic Effects

CHANTRAPA SRISWASDI, M.D.*, SAENGSUREE JOOT AR, M.D.**, FRANCIS J. GILES, M.D.***

Affiliation : * Department of Medicine, Pramongkutklao Hospital, Bangkok 10400, ** Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Bangkok 10400, Thailand. *** Department of Leukemia, M.D. Anderson Cancer Center, Houston, Texas 77030, U.S.A.

AbstractAmifostine is a protective agent of normal tissue from adverse effects of radiochemo- therapy. It is the prodrug that is dephosphorylated by alkaline phosphatase on plasma membrane into the active form named WR-1065. More than 90 per cent of the drug is cleared from plasma in 6 minutes and the peak tissue concentration is 10-30 minutes after intravenous administration. Amifostine has the selective property to protect normal tissue but not cancer cells by mainly scavenging free radicals induced by radiation and chemocytotoxic agents. Both preclinical and clinical studies of this drug provide the significant protection of hematopoietic progentitors from a broad range of cytotoxic agents such as cyclophosphamide, cisplatin, vinblastine, carboplatin, mitomycin-C. fotemustine, doxorubicin, daunorubicin and radiation as well. Moreover, this drug can protect other normal organs or tissues including kidney, salivary gland, liver, heart, lung and small intestine. Amifostine is quite safe, the two major side effects are vomiting and hypotension, and the minor effects are flushing, sneezing, dizziness, chills, metallic taste etc. The drug was approved by the FDA of U.S.A. for use as a cytoprotectant in cyclophosphamide and cisplatin treatment for advanced ovarian cancer and non small cell lung cancer.

Keywords : Amifostine, Cytoprotectant

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