沙利度胺联合VAD方案治疗多发性骨髓瘤的临床研究

目的：探讨沙利度胺联合VAD方案治疗多发性骨髓瘤（MM）的临床疗效及不良反应。方法：43例MM患者。随机分为VAD方案对照组：长春新碱加阿霉素加地塞米松;治疗组：VADTY案加沙利度胺,沙利度胺100～200mg,d,每晚1次,维持该剂量半年。结果：治疗组部分缓解5例（22．73％）,进步12例（54．55％）,无效5例（22．72％）,总有效率77．28％（17／22）。明显优于对照组（总有效率的47．62％）（P〈0．05）;能有效降低M蛋白,使骨髓瘤细胞下降,提升血红蛋白和改善生活自理状况（P〈0．05）;不良反应程度均可耐受。结论：沙利度胺联合VAD方案治疗MM具有不良作用少、耐受性好、给药方便、疗效明显的优点,值得临床深入研究和推广应用。     

不同方案治疗多发性骨髓瘤120例疗效观察

目的探讨不同化疗方案对多发性骨髓瘤(MM)患者的治疗效果。方法回顾分析120例MM患者,其中40例患者接受沙利度胺加硼替佐米联合地塞米松(BD)方案治疗,40例患者接受沙利度胺加长春新碱联合阿霉素、地塞米松(VAO)方案化疗,另40例患者接受BD(硼替佐米联合地塞米松)方案治疗;所有患者均接受4～6个疗程治疗后进行全面评价,自动放弃治疗、疗程不符合标准以及失访患者不计入。结果沙利度胺+BD组、沙利度胺+VAD组和BD组的总完全缓解(TR)率分别为65%、40%和35%,3组比较差异均有显著性(P<0.05);3组的总体有效(RR)率分别为85%、62.5%和60%,3组比较差异无显著性(P>0.05)。常见的不良反应有骨髓抑制、消化道症状、肝肾功能损害、周围神经病变、乏力、血栓形成、血凝异常、带状疱疹病毒感染、精神症状、皮疹等,3组比较差异无显著意义(P>0.05)。结论沙利度胺加BD方案联合治疗MM具有不良反应少、耐受性好、疗效明显等优点。     

沙利度胺治疗消化道疾病的研究进展

随着科学的进步,消化道疾病的治疗研究不断发展。近年来,病例报道和临床试验都证明沙利度胺正在作为一种有效、可供选择的药物用以治疗消化道疾病。除了可以部分下调促炎症介质肿瘤坏死因子α（TNF-α）,抑制由血管内皮生长因子（VEGF）和碱性纤维母细胞生长因子（bFGF）诱导的血管增生,沙利度胺还具有其他免疫调节特性。本文就沙利度胺治疗消化道疾病进行综述。     

Enhancement of cisplatin efficacy by thalidomide in a 9L rat gliosarcoma model

With the aim of improving the treatment of glioblastoma multiforme, we investigated the potential of thalidomide to enhance the effectiveness of cisplatin chemotherapy in a rat glioma model. Female F344 rats were implanted with 9L gliosarcoma tumors either intracranially or subcutaneously and treated with 1 mg/kg cisplatin injected i.p. or with 1% thalidomide in the food or with these treatments combined. Cisplatin in combination with thalidomide significantly reduced both the subcutaneous tumor volume at 30 days to 22 ± 5% (mean ± SEM, P < 0.001) and the intracranial tumor volume at 18 days to 44 ± 15% (P < 0.05) of that with cisplatin alone. Thalidomide selectively increased the cisplatin concentration 10–fold in intracranial tumors (P < 0.05) and 2-fold in the subcutaneous tumors (P < 0.05) without increasing its concentration in major organs including brain and kidney. Cisplatin combined with thalidomide caused a significant decrease in vascular endothelial growth factor (VEGF) levels by 73% in intracranial tumors (P < 0.05) and by 50% in subcutaneous tumors (P < 0.05) and caused the level of active hepatic growth factor (a-HGF) to double in both the subcutaneous and intracranial tumors (P < 0.05), suggesting this treatment altered the vasculature in these tumors. We conclude the increased efficacy of cisplatin in the presence of thalidomide was due to the selective increase in cisplatin concentration within the tumors and speculate that this is the result of thalidomide or the cisplatin/thalidomide combination, selectively altering the tumor vasculature. Based on the selective effects of thalidomide on tumor cisplatin concentrations and the resulting increase in efficacy, thalidomide may also increase the efficacy of other drugs that are presently considered ineffective against glioma.     

A phase II study of extended dose temozolomide and thalidomide in previously treated patients with metastatic melanoma

Purpose To assess the efficacy and tolerability of extended dose temozolomide and continuous thalidomide in patients with advanced metastatic cutaneous melanoma.Patients and methods Eligibility criteria included adults with histologic diagnosis of metastatic melanoma with adequate organ function and performance status. Temozolomide (75 mg/m²/day) was administered for 6 weeks followed by a 2-week rest. Thalidomide (200 mg/day) was given for the first 2 weeks and increased by 100 mg/day at weekly intervals up to a maximum of 400 mg/day, if no toxicity. For patients older than 70 years, thalidomide was started at 100 mg/day and the dose was increased by 50 mg/day up to a maximum of 250 mg/day.Results Twenty-six extensively pretreated subjects, with poor prognostic factors, were entered into this study and included in all analyses. According to the RECIST criteria, one (4%) subject achieved a complete response (CR), two (8%) partial response (PR), and five (19%) stable disease (SD), for a response rate (CR + PR) of 12% [95% confidence interval (CI), 0–24.7%] and a clinical benefit (CR + PR + SD) of 31%. Median time to progression was 1.8 months (95% CI, 1.2–2.4 months) and median survival was 5.2 months (95% CI, 4.1–6.2 months).Conclusions The combination of temozolomide and thalidomide is well tolerated in patients with very advanced heavily pretreated metastatic melanoma. It has modest activity in this population with grave prognosis.     

5′-Substituted Thalidomide Analogs as Modulators of TNF-α

The synthesis of 5′-substituted thalidomide analogs is described. The amino acids 2 necessary to synthesize the target compounds were prepared by Michael reaction. Condensation of 2 with phthalic anhydrides followed by reaction with urea yielded 4 as diastereomeric mixtures. Furthermore glutethimide ( 5 ) was brominated by an improved method and the resulting compound 6 was reacted in several steps with sodium azide, hydrogen, and phthalic anhydride to give 8 . In a similar manner, 6 was reacted with sodium azide and various phthalic anhydrides to give 9 , 10 , and 11 . All final compounds were tested in vitro for their inhibitory activity on the release of TNF-α, using stimulated peripheral mononuclear blood cells (PBMCs). Compounds with an additional aromatic substituent in position 5’ of the thalidomide molecule were more active than thalidomide. Compound 11 was able to reduce increased levels of IL-2 in vitro.     

利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤的疗效评价

目的评价利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)的有效性及安全性。方法回顾性分析甘肃省武威肿瘤医院血液科使用R-CHOP方案化疗后完全缓解的≥60岁的DLBCL患者86例,按其治疗方案分为2组。对照组患者在完全缓解后单用利妥昔单抗维持治疗(n=43);治疗组患者应用利妥昔单抗联合沙利度胺方案维持治疗(n=43例)。对两组患者的预后进行分析。结果治疗组4年、5年总生存期(OS)率高于对照组(P<0.01);3年、4年、5年无进展生存期(PFS)率高于对照组(P<0.01);治疗组总生存时间、无进展生存时间明显长于对照组(P<0.001)。结论利妥昔单抗联合沙利度胺维持治疗老年人DLBCL,可延长患者总生存时间及无进展生存时间,无严重不良反应发生。     

Effect of different doses of dexamethasone combined with bortezomib and thalidomide in treatment of elderly patients with multiple myeloma

Objective: To observe the efficacy and safety of different doses of dexamethasone combined with bortezomib and thalidomide in the treatment of elderly patients with multiple myeloma (MM). Methods: A total of 33 elderly MM patients treated in Shanghai Fifth People's Hospital between August 2014 and August 2019 were enrolled in the study. According to the dosage of dexamethasone, the patients were divided into the observation group (low dose dexamethasone, 20 mg/d on day 1-4, and 11-14) and the control group (high dose dexamethasone, 40 mg/d on day 1-4, 9-12, and 17-20). Twenty-eight days was a course of treatment. The clinical efficacy and safety of patients was assessed after 4 courses of treatment. The patients were followed up till June 30th, 2021. Kaplan-Meier and log-rank were used to analyze the survival. Results: The overall response rate (ORR) and median overall survival (OS) were not significantly different between the observation and control groups (82.4% vs 87.5%, P=0.973; 58 months vs 61 months, P=0.859). The incidence rates of lung infection and hyperglycemia in the observation group were both significantly lower than those in the control group (both P< 0.05). Conclusions: Different doses of dexamethasone combined with bortezomib and thalidomide have definite curative effects in the treatment of elderly MM patients. But low dose dexamethasone has fewer adverse reactions and better safety. © 2022, The Second Affiliated Hospital, College of Medicine, Zhejiang University.. All right reserved.