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首页> 外文期刊>Japanese Journal of Cancer Research >Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome.
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Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome.

机译：沙利度胺治疗难治性多发性骨髓瘤：沙利度胺的血浆浓度和血管生成因子与临床结果的关联。

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Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2 - 4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (2.0 &mgr;g/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P = 0.025), but not in non-responders (P = 0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide.
机译：最近的报道表明，沙利度胺具有抗血管生成活性，对难治性多发性骨髓瘤（MM）有效。我们检查了沙利度胺的临床疗效和不良反应与该药物的血浆浓度以及难治性MM的血管生成生长因子之间的关系。 24名可评估患者中有10名（42％）的M蛋白减少量超过25％，八名（33％）的M蛋白减少量超过50％。这些变化与贫血的恢复和正常免疫球蛋白水平的恢复有关。经常观察到嗜睡和头痛，便秘，周围神经病变和皮疹，但耐受性良好。但是，在9例患者中也观察到2-4级严重中性粒细胞减少。除中性粒细胞减少症外，这些不良反应在沙利度胺血浆浓度较高（最后一次给药后12 h为2.0μg/ ml）的患者中更常见，并且可通过降低剂量轻松缓解。相反，无论血浆浓度如何，都会出现中性粒细胞减少症。在治疗前，血浆中血管生成生长因子的浓度经常升高。沙利度胺治疗后，这些生长因子水平在应答者中趋于降低至接近正常范围，但在大多数非应答者中仍较高。沙利度胺治疗后，反应者的血浆血管内皮生长因子（VEGF）水平显着降低（P = 0.025），而非反应者则没有（P = 0.37）。血浆VEGF水平的降低可能是沙利度胺抗骨髓瘤作用的重要指标。

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