Kurbacher C M, Mallmann P K
Department of Gynecology and Obstetrics, University of Cologne Medical Center, Germany.
Anticancer Res. 1998 May-Jun;18(3C):2203-10.
Amifostine (WR-2721, Ethyol), S-2[3-aminopropylamino]-ethyl-phosphorothioic acid, was selected as a clinically usable radioprotector from more than 4,400 compounds in the 1950s. A considerable amount of preclinical work suggested that amifostine, or its activated thiol WR-1065, protected normal cells effectively against the adverse effects of irradiation and several anticancer drugs without exhibiting tumor protection. In non-randomized and randomized trials in malignant melanoma, colorectal cancer, head and neck cancer, non-small cell lung cancer, and epithelial ovarian carcinoma, amifostine significantly reduced the hematological and non-hematological toxicity of DNA-damaging agents such as alkylators, platinum compounds, or mitomycin C. In more recent studies, the drug also protected patients from side effects produced by taxanes or topoisomerase I inhibitors and is thus likely to allow higher cytostatic doses to be administered. Currently, there is no evidence that amifostine compromises the antineoplastic effect of the drugs studied. Otherwise, W/R-2721 may even improve the therapeutic efficacy of agents like cisplatin, carboplatin, or paclitaxel. Moreover, amifostine appears to produce growth-factor like properties resulting in growth-promoting effects on primitive blood progenitor cells ex vivo. Amifostine offers a rational approach to protect patients against chemotherapy-specific and often dose-limiting effects and is thus likely to improve therapeutic outcome significantly. Future studies should be focused on both new indications like childhood cancer, myelodysplastic syndromes, dose-intensified or high- dose chemotherapy, and multimodality approaches and optimization of amifostine dosage in order to reduce dose-limiting side effects. Then, the drug may play a major role in more specific and individualized oncologic strategies.
氨磷汀（WR-2721，依硫醇），即S-2[3-氨丙基氨基]-乙基硫代磷酸，是在20世纪50年代从4400多种化合物中筛选出的一种临床可用的辐射防护剂。大量临床前研究表明，氨磷汀或其活性硫醇WR-1065可有效保护正常细胞免受辐射及多种抗癌药物的不良影响，而对肿瘤细胞无保护作用。在恶性黑色素瘤、结直肠癌、头颈癌、非小细胞肺癌和上皮性卵巢癌的非随机和随机试验中，氨磷汀显著降低了烷化剂、铂类化合物或丝裂霉素C等DNA损伤剂的血液学和非血液学毒性。在最近的研究中，该药物还能保护患者免受紫杉烷类或拓扑异构酶I抑制剂产生的副作用影响，因此有可能允许给予更高的细胞毒性剂量。目前，没有证据表明氨磷汀会削弱所研究药物的抗肿瘤作用。此外，WR-2721甚至可能提高顺铂、卡铂或紫杉醇等药物的治疗效果。此外，氨磷汀似乎具有生长因子样特性，在体外对原始血液祖细胞产生促生长作用。氨磷汀为保护患者免受化疗特异性且常为剂量限制性的影响提供了一种合理方法，因此有可能显著改善治疗效果。未来的研究应聚焦于儿童癌症、骨髓增生异常综合征等新适应症、剂量强化或高剂量化疗、多模式方法以及氨磷汀剂量的优化，以减少剂量限制性副作用。届时，该药物可能在更具特异性和个体化的肿瘤治疗策略中发挥重要作用。
