Antitumor activity of thalidomide in refractory multiple myeloma.
Antitumor activity of thalidomide in refractory multiple myeloma.
复制标题
DOI：
10.1056/nejm199911183412102
复制
发表时间：
1999-11-18
影响因子：
158.5
通讯作者：
Crowley, J
中科院分区：
文献类型：
--
作者：
Singhal, S;Mehta, J;Crowley, J
背景：大剂量化疗后复发的骨髓瘤患者几乎没有治疗选择。由于骨髓血管增多导致骨髓瘤预后不良，我们评估了具有抗血管生成特性的沙利度胺在难治性疾病患者中的疗效。方法：84例既往治疗的难治性骨髓瘤患者(76例大剂量化疗后复发)接受沙利度胺单药治疗，中位时间为80天(范围2~465天)。起始剂量为200 mg/d，以后每2周增加200 mg，至800 mg/d。结果：8例患者血清或尿液副蛋白水平下降至少90%(2例完全缓解)，6例患者血清或尿液副蛋白水平下降至少75%，7例患者下降至少50%，6例患者下降至少25%，总有效率32%。在78%的有反应的患者中，副蛋白水平在两个月内明显下降，并与骨髓中浆细胞数量的减少和血红蛋白水平的上升有关。有反应的患者骨髓微血管密度无明显变化。至少三分之一的患者有轻度或中度便秘、虚弱或疲劳或嗜睡。更严重的不良反应很少发生(发生在不到10%的患者中)，血液学影响也很少见。截至最近的随访，36名患者死亡(30名无反应，6名有反应)。经过12个月的随访，Kaplan-Meier估计所有患者的平均(+/-SE)无事件生存率和总生存率分别为22+/-5%和58+/-5%。结论：沙利度胺对晚期骨髓瘤有效。它可以在一些多发性骨髓瘤患者中诱导显著和持久的反应，包括那些在大剂量化疗后复发的患者。(N Engl J Med 1999；341：1565-71)(C)1999年，马萨诸塞州医学会。
Background: Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options. Since increased bone marrow vascularity imparts a poor prognosis in myeloma, we evaluated the efficacy of thalidomide, which has antiangiogenic properties, in patients with refractory disease.Methods: Eighty-four previously treated patients with refractory myeloma (76 with a relapse after high-dose chemotherapy) received oral thalidomide as a single agent for a median of 80 days (range, 2 to 465). The starting dose was 200 mg daily, and the dose was increased by 200 mg every two weeks until it reached 800 mg per day. Response was assessed on the basis of a reduction of the myeloma protein in serum or Bence Jones protein in urine that lasted for at least six weeks.Results: The serum or urine levels of paraprotein were reduced by at least 90 percent in eight patients (two had a complete remission), at least 75 percent in six patients, at least 50 percent in seven patients, and at least 25 percent in six patients, for a total rate of response of 32 percent. Reductions in the paraprotein levels were apparent within two months in 78 percent of the patients with a response and were associated with decreased numbers of plasma cells in bone marrow and increased hemoglobin levels. The microvascular density of bone marrow did not change significantly in patients with a response. At least one third of the patients had mild or moderate constipation, weakness or fatigue, or somnolence. More severe adverse effects were infrequent (occurring in less than 10 percent of patients), and hematologic effects were rare. As of the most recent follow-up, 36 patients had died (30 with no response and 6 with a response). After 12 months of follow-up, Kaplan-Meier estimates of the mean (+/-SE) rates of event-free survival and overall survival for all patients were 22+/-5 percent and 58+/-5 percent, respectively.Conclusions: Thalidomide is active against advanced myeloma. It can induce marked and durable responses in some patients with multiple myeloma, including those who relapse after high-dose chemotherapy. (N Engl J Med 1999;341:1565-71.) (C) 1999, Massachusetts Medical Society.