Rick O, Beyer J, Schwella N, Schubart H, Schleicher J, Siegert W
Klinik für Innere Medizin m. S. Hämatologie/Onkologie, Universitatsklinikum Charité, Humboldt Universität, Berlin, Germany.
Ann Oncol. 2001 Aug;12(8):1151-5. doi: 10.1023/a:1011628900089.
We assessed the efficacy of amifostine for protection from chemotherapy-induced toxicities in patients treated with conventional-dose paclitaxel, ifosfamide, cisplatin (TIP) and high-dose carboplatin, etoposide and thiotepa (CET) followed by peripheral blood progenitor cell (PBPC) rescue.
In a prospective single-center study 40 patients with relapsed or refractory germ-cell tumors (GCT) were treated with 3 cycles of conventional-dose TIP followed by one cycle of high-dose CET. Patients were randomized either to receive one fixed dose of 500 mg amifostine per day of conventional-dose TIP and two fixed doses of 500 mg per day amifostine during high-dose CET (group A, n = 20) or no amifostine (group B, n = 20). Prior to the first cycle of TIP, one course of 175 mg/m2 paclitaxel and 5 g/m2 ifosfamide (TI) followed by granulocyte-colony stimulating factor (G-CSF) at 10 microg/kg/day were given for PBPC mobilization.
Toxicities and response to conventional-dose TIP and high-dose CET could be evaluated in 40 patients (100%) and 32 of 40 patients (80%), respectively. Peripheral neurotoxicity (i.e. paresthesia or sensorymotor impairment), hearing impairment, hematologic toxicity, nephrotoxicity, nausea, myalgia, skin- and liver-toxicity did not differ siginificantly between the two patient groups. Likewise, the response rates to TIP and high-dose CET were comparable in patients with or without amifostine. After a median follow-up of 18 months, 8 of 20 (40%) patients of group A and 6 of 20 (30%) patients of group B are without relapse.
Repeated low doses of 500 mg amifostine additional to conventional-dose TIP or high-dose CET showed no unequivocal advantage in protection from treatment-related toxicities. Furthermore, no significant differences in response rates or survival could be observed in this small number of patients.
我们评估了氨磷汀对接受常规剂量紫杉醇、异环磷酰胺、顺铂（TIP）以及大剂量卡铂、依托泊苷和塞替派（CET）治疗后行外周血祖细胞（PBPC）解救的患者化疗所致毒性的保护作用。
在一项前瞻性单中心研究中，40例复发或难治性生殖细胞肿瘤（GCT）患者接受3个周期的常规剂量TIP治疗，随后接受1个周期的大剂量CET治疗。患者被随机分为两组，一组在常规剂量TIP治疗期间每天接受固定剂量500mg氨磷汀，在大剂量CET治疗期间每天接受两个固定剂量500mg氨磷汀（A组，n = 20），另一组不接受氨磷汀治疗（B组，n = 20）。在TIP的第一个周期之前，给予一个疗程的175mg/m²紫杉醇和5g/m²异环磷酰胺（TI），随后给予粒细胞集落刺激因子（G-CSF），剂量为10μg/kg/天，用于PBPC动员。
分别有40例患者（100%）和40例患者中的32例（80%）可评估常规剂量TIP和大剂量CET的毒性及反应。两组患者在外周神经毒性（即感觉异常或感觉运动障碍）、听力损害、血液学毒性、肾毒性、恶心、肌痛、皮肤和肝脏毒性方面无显著差异。同样，接受或未接受氨磷汀治疗的患者对TIP和大剂量CET的反应率相当。中位随访18个月后，A组20例患者中有8例（40%）无复发，B组20例患者中有6例（30%）无复发。
在常规剂量TIP或大剂量CET基础上重复给予低剂量500mg氨磷汀，在预防治疗相关毒性方面未显示出明确优势。此外，在这少数患者中未观察到反应率或生存率的显著差异。
