聚焦多发性骨髓瘤

虽然免疫抑制剂和蛋白酶体抑制剂的应用使多发性骨髓瘤治疗领域在过去10年取得了显著进展率最低的癌症之一。多发性骨髓瘤目前仍不可治愈,甚至连有效地维持缓解都极为困难。复杂的临床表现、比较研究数据的缺乏导致这一疾病的治疗变得更加复杂。但该疾病仍是预后差且5年存活多样的治疗选择以及长期、大规模受性方面均有显著提高,并且已通过加快审批通道进入市场,用于曾接受过多次既往治疗的患者,治疗复发性／难治性多发性骨髓瘤,但目前还未获得其完整的存活率数据。在基因组学领域,已开始对患者进行更加个体化的预后和治疗,然而这一领域还仅仅处于起步阶段。随着多发性骨髓瘤发生机制的进一步阐明以及竞争前研究合作的进一步加强,希望能够在这一治疗需求远远未被满足的领域快速研发出新—代靶向治疗药物。     

门诊沙利度胺超说明书使用的评价及管理

目的 通过循证医学的方法评价和规范沙利度胺的合理化用药。方法 回顾性调取2017年沙利度胺片处方122张,对超说明书用药的处方进行分类统计,并寻找中外数据库、典籍、指南等循证依据,依照证据质量提出超说明书用药的推荐强度和干预措施。结果 沙利度胺片超说明书使用的主要类型为超适应证,发生率最高的前3位科室分别为血液科、风湿免疫科和口腔科,发生率最高的前3位临床疾病分别为多发性骨髓瘤、原发性骨髓纤维化和复发性阿弗他溃疡。根据超说明书用药分级管理制度,对超说明书用法进行循证分析,同意使用的有1种,限制使用的有5种,特殊使用的有5种,不同意使用的有0种。结论 沙利度胺片超说明书用药现象普遍存在,应严格执行超说明用药制度,促进临床用药安全。     

Real‐world health care costs of relapsed/refractory multiple myeloma during the era of novel cancer agents

What is known and objective: High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real‐world costs and cost‐effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real‐world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice. Methods: A retrospective medical chart review was conducted for 139 patients treated between January 2001 and May 2009. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib‐, thalidomide‐ and lenalidomide‐based treatment regimens. Results: Mean monthly total costs (€3,981) varied depending on the sequence of therapy (range: €442–€31,318). Significant cost drivers across all regimens included costs of therapy and hospital admissions. The acquisition costs for novel agents in particular accounted for 32% of mean total monthly costs. Prognostic factors associated with increased mean total monthly costs in multivariate regression analysis included low platelet counts (P = 0·01) and worsening performance status (P < 0·001). Mean total monthly costs of bortezomib‐ and lenalidomide‐based regimens were significantly higher than those for thalidomide‐based regimens in second, third and fourth treatment line. What is new and conclusions: Real‐world costs during treatment of relapsed/refractory multiple myeloma vary greatly. Cost drivers include hospital admissions and acquisition costs of novel agents. Costs also vary by prognostic factors and treatment‐related resource use. Future studies assessing the costs of combination therapy consisting of two or more novel agents are encouraged.     

Effects of thalidomide on DMBA-induced oral carcinogenesis in hamster with respect to angiogenesis

Background:  Thalidomide has been shown to have anti-angiogenic effects in pre-clinical models as well as a significant antitumor effect in hematologic tumors. However, the effects of thalidomide on oral pre-malignant lesions and oral carcinogenesis remain unexplored. The authors aimed to investigate the chemopreventive effect of thalidomide on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters with respect to angiogenesis.
Methods:  Seventy male Syrian golden hamsters were randomly divided into five groups, with two of 20 and three of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek pouch of male Syrian golden hamsters in group A and B, while animals in group C were painted with acetone, three times a week for 6 weeks. For the next 18 weeks, animals in group B and D received thalidomide daily (40 mg/kg body weight/day) by gavage, animals in group A and C received same volume of saline. Animals in group E received no treatment and served as blank control. At the end of the experiment, animals were killed and tissue samples were collected for examinations.
Results:  Thalidomide significantly decreased the squamous cell carcinoma (SCC) incidence from 57.9 to 11.8%; angiogenesis was inhibited in dysplasia and SCC. The gene expression of vascular endothelium growth factor and tumor necrosis factor (TNF)-α was downregulated.
Conclusions:  Thalidomide has inhibitory effect against the malignant transformation of oral pre-cancerous lesion and angiogenesis during oral carcinogenesis. Such inhibition is related to its modulation of TNF-α.     

沙利度胺治疗恶性肿瘤的研究进展

沙利度胺早期作为一种非巴比妥类镇静剂用于早孕反应的治疗，但由于严重的致畸作用而被禁用。随后的研究发现，沙利度胺具有抑制肿瘤坏死因子-α（TNF-α）作用，1998年美国FDA批准其用于麻风病结节性红斑的治疗。近年来研究发现，沙利度胺具有抗血管生成及调节免疫等作用。目前，沙利度胺已经成为复发和难治性骨髓瘤标准治疗的一部分，和其他药物联合应用对其他实体肿瘤如神经胶质细胞瘤、前列腺癌、肾癌、恶性黑色素瘤和肺癌等的治疗显示一定效果，但其作用机制尚不完全明了。     

沙利度胺辅助化疗治疗晚期非小细胞肺癌

目的 观察沙利度胺辅助化疗对晚期非小细胞肺癌(NSCLC)的治疗作用. 方法 40例Kamofsky评分达到60分以上的NSCLC患者,随机分为治疗组(n=20)和对照组(n=20).治疗组接受化疗联合沙利度胺治疗,对照组则仅接受化疗,两组化疗方案均为长春瑞滨+卡铂.以近期有效率和中位缓解期评价各组疗效.结果 治疗组近期有效率和中位缓解期分别为61.1%和2.7月,对照组相应的为50.0%和2.4月,两组相比无显著差异(P>0.05).结论 沙利度胺辅助化疗用于晚期NSCLC耐受性良好,并具有一定的增效减毒作用.     

沙利度胺与地塞米松联合治疗多发性骨髓瘤的临床研究

目的 探讨沙利度胺与地塞米松联合治疗多发性骨髓瘤(MM)的临床疗效及不良反应.方法 39例初治MM患者,随机分为两组,VAD方案对照组:长春新碱加阿霉素加地塞米松;治疗组:沙利度胺加地塞米松,沙利度胺起始剂量为100～200 mg/d,以后每周加量50～100 mg/d,最大剂量400 mg/d,并加用地塞米松20 mg/(m2. d),第1～4天,第9～12天,第17～20天,30天后重复上述方案,至少治疗3个月.结果 治疗组部分缓解9例(45.0%),进步6例(30.0%),无效5例,总有效率75.0%(15/20),明显优于对照组(总有效率52.6%)(P＜0.05);能有效降低M蛋白,使骨髓瘤细胞下降,提高血红蛋白和改善生活自理状况(P＜0.05).副反应程度均可耐受.结论 沙利度胺联合地塞米松治疗多发性骨髓瘤(MM)具有副作用少、耐受性好、给药方便、费用低、疗效明显的优点,值得临床推广应用.