A phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy
A phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy
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DOI：
10.1007/s00280-001-0417-z
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发表时间：
2002-04-01
影响因子：
3
通讯作者：
Mickisch, GHJ
中科院分区：
文献类型：
--
作者：
Vis, AN;van der Gaast, A;Mickisch, GHJ
导言：肾细胞癌(RCC)在转移到远处时预后很差，尽管免疫治疗可以延长特定患者组的生存期。不幸的是，当免疫疗法失败时，就没有治疗选择了。在这项IIa期试验中，我们评估了抗叶酸药甲氨蝶呤-人血清白蛋白(MTX-HSA)在一线免疫治疗后进展的转移性肾癌患者中的耐受性和疗效。患者和方法：共有17名患者开始治疗，其中14名(男性12名，女性2名)根据IIa Gehan期设计可评价疗效。这些患者有肿瘤肾切除史，总体状况相对较好，没有肾、肝或骨髓功能损害，在接受干扰素-α联合或不联合顺式维甲酸治疗后有进展性转移疾病(EORTC方案30951和30947)。甲氨蝶呤-人血清白蛋白(MTX-HSA)在门诊基础上每周静脉注射一次，剂量为50 mg/m(2)。对于那些尚未从既往毒性中恢复的患者，治疗间隔时间延长。结果：大多数病例毒性可控，相对轻至中度，且可逆。最常见的是2/3级粘膜炎(10/17)和3级转氨酶升高(4/17)，只有1例患者报告为4级血小板减少。三个无法评估的病人。1例因与药物有关的毒性而停止治疗。平均给药间隔为12.1天，14名可评估患者中有7名的治疗间隔为1周或2周。虽然8名患者病情稳定(稳定2个月)长达8个月(中位数121天)，但未见客观反应。结论：MTX-HSA耐受性良好，可在门诊使用，但在既往免疫治疗后进展的转移性肾癌患者中未见客观反应。
Introduction: Renal cell carcinoma (RCC) has a poor prognosis when metastasized to distant sites, although immunotherapy may offer a prolongation of survival in selected patient groups. Unfortunately, no treatment options remain when immunotherapy fails. In this phase IIa trial the tolerability and efficacy of the antifolate drug methotrexate-human serum albumin (MTX-HSA) were evaluated in patients with metastatic RCC who progressed after first-line immunotherapy. Patients and methods: A total of 17 patients started treatment, and 14 (12 men, 2 women) were evaluable for response according to the phase IIa Gehan design. Patients had prior tumor nephrectomy, were in relatively good general condition, had no impairment of renal, liver or bone marrow function, and had progressive metastatic disease after treatment with interferon-alpha (IFN-alpha) with or without cis-retinoic acid (EORTC protocols 30951 and 30947). MTX-HSA was given once a week intravenously on an outpatient basis at a dose of 50 mg/m(2). The treatment interval was prolonged in those patients who had not yet recovered from previous toxicities. Results: Toxicity was manageable, relatively mild to moderate and reversible in most cases. Grade 2/3 mucositis (10/17) and grade 3 elevated transaminase levels (4/17) were most frequent, and in only one patient was a grade 4 thrombocytopenia reported. Of three inevaluable patients. one discontinued treatment due to drug-related toxicities. The mean administration interval was 12.1 days, and 7 of 14 evaluable patients had treatment intervals of I or 2 weeks. No objective responses were seen, although eight patients had stable disease (stabilization >2 months) for up to 8 months (median 121 days). Conclusion: MTX-HSA was generally well tolerated and can be given on an outpatient basis, but no objective responses were seen in patients with metastatic RCC who had progressed after previous immunotherapy.