Amifostine and hematologic effects.
Amifostine is a protective agent of normal tissue from adverse effects of radiochemotherapy. 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.
Sriswasdi
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C
Department of Medicine, Pramongkutklao Hospital, Bangkok, Thailand.
Jootar
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S
Giles
F J
FJ
D004999:Amifostine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006402:Hematologic Diseases / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007262:Infusions, Intravenous; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D011878:Radiotherapy / Q000009:adverse effects*; D012680:Sensitivity and Specificity
D011837:Radiation-Protective Agents; D004999:Amifostine