Mohr P, Makki A, Breitbart E, Schadendorf D
Dermatologisches Zentrum Buxtehude, Universität Heidelberg, Germany.
Melanoma Res. 1998 Apr;8(2):166-9. doi: 10.1097/00008390-199804000-00011.
Amifostine (Ethyol) is a new chemoprotective agent that has been shown to have significant activity in the prevention of nephro-, oto-, neuro- and haemotoxicity. In preclinical models as well as in clinical trials carried out in patients suffering from various malignancies, the adverse effects and signs of toxicity related to a number of cytostatic drugs, including cisplatin, cyclophosphamide, carboplatin and mitomycin C, were prevented. In Europe fotemustine (Muphoran) is widely used in the treatment of brain metastases in melanoma patients. However, the dose is often limited by severe bone marrow toxicity after induction cycles, particularly in heavily pretreated patients. In order to test whether amifostine treatment might promote bone marrow protective effects when combined with fotemustine chemotherapy, we conducted a preliminary study in 10 patients suffering from stage IV disseminated malignant melanoma. The patients received amifostine (740 mg/m2) prior to fotemustine chemotherapy (100 mg/m2). Six of the patients had failed one or two other prior chemotherapy regimens. Seven patients had brain metastases. Among the 10 patients treated with amifostine and fotemustine, no major clinical responses (complete response or partial response) were achieved, with four patients showing stabilization of the disease over more than 3 months. No patient in the amifostine plus fotemustine treatment group showed severe myelosuppression (WHO grade III/IV), in contrast to a historical control group treated with fotemustine alone, in which about 40% developed major thrombocytopenia and about 45% developed severe leucopenia (WHO grade III/IV). Therefore, we conclude that the combination of amifostine with fotemustine was well tolerated in this small series of patients and further studies are warranted to test the amelioration of myelosuppression by the addition of amifostine.
氨磷汀（Ethyol）是一种新型化学保护剂，已显示出在预防肾毒性、耳毒性、神经毒性和血液毒性方面具有显著活性。在临床前模型以及对患有各种恶性肿瘤的患者进行的临床试验中，与多种细胞毒性药物（包括顺铂、环磷酰胺、卡铂和丝裂霉素C）相关的不良反应和毒性迹象得到了预防。在欧洲，福莫司汀（Muphoran）广泛用于治疗黑色素瘤患者的脑转移瘤。然而，诱导周期后严重的骨髓毒性常常限制了剂量，尤其是在经过大量预处理的患者中。为了测试氨磷汀治疗与福莫司汀化疗联合使用时是否可能促进骨髓保护作用，我们对10例IV期播散性恶性黑色素瘤患者进行了一项初步研究。患者在接受福莫司汀化疗（100 mg/m²）之前先接受氨磷汀（740 mg/m²）治疗。其中6例患者之前的一种或两种化疗方案治疗失败。7例患者有脑转移。在接受氨磷汀和福莫司汀治疗的10例患者中，未取得重大临床反应（完全缓解或部分缓解），4例患者疾病稳定超过3个月。与仅接受福莫司汀治疗的历史对照组相比，氨磷汀加福莫司汀治疗组中没有患者出现严重骨髓抑制（世界卫生组织III/IV级），在历史对照组中，约40%的患者出现严重血小板减少，约45%的患者出现严重白细胞减少（世界卫生组织III/IV级）。因此，我们得出结论，在这一小系列患者中，氨磷汀与福莫司汀联合使用耐受性良好，有必要进一步研究以测试添加氨磷汀对骨髓抑制的改善作用。
