eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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2/2004
vol. 8
 
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abstract:

Amifostine: a cytoprotective drug

Jadwiga Dwilewicz-Trojaczek

Współcz Onkol (2004) vol. 8; 2 (101–106)
Online publish date: 2004/03/15
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Amifostine (WR-2721, Ethyol, 2-[(3-aminopropyl) amino]-ethylphosphorothioic amid) is an inorganic thiophosphate. It is a prodrug that is dephosphorylated to active metabolite known as WR-1065 by the plasma membrane-bound enzyme, alkaline phosphatase. Protection of cell damage by WR-1065 is thought to occur through scavenging oxygen-derived free radicals and hydrogen donation to repair damaged target molecules. The mechanism by which amifostine exerts its selective protection of normal tissue is based on the ability of free thiol to be taken up in higher concentration by normal organs than by tumor tissue. Clinical trials with amifostine were initiated in the 1980s. Acceptable tolerated dose was established for use in phase II studies, which ranged from 740 mg/m2 to 910 mg/m2. Amifostine is generally well-tolerated. The most clinically significant toxicity is hypotension (<5%). The recommended dose of amifostine combined with radiation therapy is 200 mg/m2, 15 to 30 minutes before each fraction of radiation therapy. Amifostine significantly reduced radiotherapy-induced acute xerostomia and late-effect xerostomia in patients with head and neck cancer. Amifostine prevents platinum toxicity: nephrotoxicity. Amifostine reduces alkylating agents-related neutropenia. Data are insufficient to recommend amifostine for the protection of cisplatin-related thrombocytopenia, neurotoxicity and ototoxicity and for the prevention of paclitaxel-related neurotoxicity. Because amifostine appears to be a broad-spectrum cytoprotective agent with the ability to protect tissues from damage induced by irradiation and chemotherapy, it may enable intensification of chemoradiation regimens. Numerous clinical trials have failed to support worries that amifostine may also reduce of anti-tumor effectiveness of radio- and chemotherapy.
keywords:

amifostine, cytoprotection, radiotherapy, chemotherapy

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