Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study
Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study
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DOI：
10.1590/s0100-879x2000000700009
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发表时间：
2000-07-01
影响因子：
2.3
通讯作者：
Damasio, E
中科院分区：
文献类型：
--
作者：
De Souza, CA;Santini, G;Damasio, E
临床试验表明，氨磷汀可能对多种正常组织具有保护作用，而不会减弱抗肿瘤反应。如果在化疗或放疗之前使用，它可以提供广泛的细胞保护，包括对烷基化药物的保护。其保护机制与膜结合碱性磷酸酶在正常组织部位的代谢有关。本品毒性中等，可出现低血压、恶心、呕吐和低钙血症。我们报告了一项II期研究，使用氨磷汀作为高剂量环磷酰胺（HDCY） （7 g/m(2)）的保护药物，用于动员外周血祖细胞（PBPC）并减轻肿瘤负担。我们招募了29例患者，22例（75.9%）为侵袭性非霍奇金淋巴瘤（NI-IL）， 7例（24.1%）为惰性非霍奇金淋巴瘤（NI-IL），这些患者接受58次氨磷汀输注，并将其与历史上侵袭性非霍奇金淋巴瘤（NI-IL）患者（33例）进行比较。支持氨磷汀的最重要的结果是降低了心脏、肺和肝毒性的强度，显著降低了粘膜炎的频率和严重程度（P = 0.04）。保护组29例患者无死亡，而历史组2/33例患者死于心脏或肺毒性，2例患者因毒性停止治疗。氨磷汀不能阻止HDCY后的再生期。两组PBPC采集和血液学恢复均足够。氨磷汀组分离产物中CFU-GM（集落形成单位-粒细胞/巨噬细胞）集落和单核细胞数量显著高于对照组（P = 0.02和0.01）。副作用轻微，易于控制。我们的结论是氨磷汀保护在HDCY中应该是有用的，以保护正常组织，副作用是可以接受的。
Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m(2)), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75.9%) affected by aggressive and 7 (24.1%) by indolent non-Hodgkin's lymphoma (NI-IL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.