Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, China.
J BUON. 2020 Nov-Dec;25(6):2608-2615.
Purpose: To investigate the clinical therapeutic effect and safety of thalidomide combined with temozolomide (TMZ) and three-dimensional conformal radiotherapy for patients with high-grade gliomas after operation.
Methods: The clinical data of 108 patients with high-grade gliomas undergoing operation in our hospital from September 2014 to December 2016 were retrospectively analyzed, of which 54 received thalidomide combined with TMZ and three-dimensional conformal radiotherapy (thalidomide group) and 54 received TMZ combined with three-dimensional conformal radiotherapy (control group). The clinical data of all patients were collected, and the short-term therapeutic effect, adverse reactions after treatment and quality of life scores were compared between the two groups of patients. Thereafter, the level of serum immune factors of the patients was recorded, and the overall survival (OS) rate and progression-free survival (PFS) rate of the patients were followed up and recorded.
Results: The therapeutic effect was evaluated in all the patients at 1 month after treatment. It was found that the overall response rate (ORR) in thalidomide group [68.5% (37/54)] was markedly higher than that in control group [44.4% (24/54)] (p=0.012), but the difference in the disease control rate (DCR) between thalidomide group [92.6% (50/54)] and control group [83.3% (45/54)] was not statistically significant (p=0.139). After treatment, the scores of 36-Item Short Form Health Survey (SF-36) evaluating the quality of life in thalidomide group were higher than that in control group, in which the physical function score was statistically significantly different between the two groups (p=0.028), whereas the scores of the other items did not statistically significantly differ between the two groups (p>0.05). Following treatment, the levels of serum hepatocyte growth factor (HGF), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-17, vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) were remarkably reduced in the two groups of patients, and these indexes in thalidomide group were lower than those in control group after treatment. Among them, HGF (p=0.069), TNF-α (p=0.076), IL-6 (p=0.149) and IL-17 (p=0.114) showed no statistically significant differences, but VEGF and EGF were statistically significantly different between the two groups (p<0.001). Moreover, adverse reactions were mainly manifested as myelosuppression, nausea and vomiting, constipation, liver function injury, drowsiness and neurotoxicity (grade I-II in most cases), which returned to normal after symptomatic treatment. Besides, the incidence rate of drowsiness of the patients in thalidomide group was notably lower than that in control group (p=0.029), but the difference in the incidence rate of other manifestations was not statistically significant (p>0.05). Additionally, the follow-up results manifested that the median OS was (16.1±3.6) months, (12.8±3.9) months, respectively, and the median PFS was (9.0±3.2) months and (12.3±3.4) months, respectively, in thalidomide group and control group. Furthermore, log-rank test revealed that the patients in thalidomide group had longer OS (p=0.025) and PFS (p=0.040) than those in control group.
Conclusions: The application of thalidomide combined with TMZ and three-dimensional conformal radiotherapy for high-grade glioma patients after operation can prominently enhance the clinical therapeutic effect, improve patient quality of life, prolong survival, and produce tolerable adverse reactions.
探讨沙利度胺联合替莫唑胺(TMZ)和三维适形放疗治疗高级别胶质瘤患者术后的临床疗效及安全性。
回顾性分析我院 2014 年 9 月至 2016 年 12 月行手术治疗的 108 例高级别胶质瘤患者的临床资料,其中 54 例采用沙利度胺联合 TMZ 和三维适形放疗(沙利度胺组),54 例采用 TMZ 联合三维适形放疗(对照组)。收集所有患者的临床资料,比较两组患者的近期治疗效果、治疗后不良反应及生活质量评分,记录患者血清免疫因子水平,随访并记录患者的总生存(OS)率和无进展生存(PFS)率。
所有患者于治疗后 1 个月进行疗效评估,结果显示沙利度胺组的总缓解率(ORR)[68.5%(37/54)]明显高于对照组[44.4%(24/54)](p=0.012),但疾病控制率(DCR)差异无统计学意义[92.6%(50/54)比 83.3%(45/54)](p=0.139)。治疗后,沙利度胺组的 36 项健康调查简表(SF-36)评估生活质量的各项评分均高于对照组,其中两组的躯体功能评分差异有统计学意义(p=0.028),而其他各项评分差异均无统计学意义(p>0.05)。治疗后,两组患者的血清肝细胞生长因子(HGF)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-17、血管内皮生长因子(VEGF)和表皮生长因子(EGF)水平均明显降低,且沙利度胺组治疗后低于对照组,其中 HGF(p=0.069)、TNF-α(p=0.076)、IL-6(p=0.149)和 IL-17(p=0.114)差异无统计学意义,而 VEGF 和 EGF 差异有统计学意义(p<0.001)。此外,不良反应主要表现为骨髓抑制、恶心呕吐、便秘、肝功能损伤、嗜睡和神经毒性(多为 I-II 级),经对症治疗后恢复正常。另外,沙利度胺组患者嗜睡的发生率明显低于对照组(p=0.029),但其他表现的发生率差异无统计学意义(p>0.05)。此外,随访结果显示,沙利度胺组的中位 OS 为(16.1±3.6)个月,中位 PFS 为(9.0±3.2)个月,对照组的中位 OS 为(12.8±3.9)个月,中位 PFS 为(12.3±3.4)个月。进一步的 log-rank 检验显示,沙利度胺组患者的 OS(p=0.025)和 PFS(p=0.040)均长于对照组。
沙利度胺联合 TMZ 和三维适形放疗治疗高级别胶质瘤患者术后可显著提高临床疗效,改善患者的生活质量,延长生存期,且产生的不良反应可耐受。