贝伐珠单抗联合替莫唑胺剂量密度方案治疗复发胶质瘤的疗效分析

目的:评价贝伐珠单抗联合替莫唑胺剂量密度方案治疗复发胶质瘤的疗效及不良事件。方法:回顾性分析20例接受过贝伐珠单抗联合替莫唑胺剂量密度方案治疗的复发胶质瘤患者的临床资料并进行生存随访。依据RANO标准评价客观疗效，应用Kaplan-Meier 法进行生存分析，不良事件评价依据CTCAE 4.0版标准。结果:20例复发胶质瘤患者的临床获益率和客观反映率可达到85%和60%，中位PFS和中位OS分别为3个月（1.5~11个月）和6.5个月（3~15个月）。主要不良事件为高血压。结论:贝伐珠单抗联合替莫唑胺剂量密度方案治疗复发胶质瘤安全有效，且耐受性良好。     

恶性脑胶质瘤术后两种同步放化疗的疗效对比

目的比较两种同步放化疗方案在恶性脑胶质瘤术后中的临床疗效。方法选取2016年1月-2017年12月我院行手术治疗的94例恶性胶质瘤患者,按随机数字表法分为A组(47例)和B组(47例),A组予以三维适行放疗与司莫司汀化疗,B组予以三维适行放疗与替莫唑胺化疗,比较不同组患者近期缓解率、远期生存率和不良反应等情况。结果B组患者近期缓解率较A组升高(P<0.05);B组治疗6个月时生存率比较差异无统计学意义(P>0.05),治疗1年时B组患者生存率较A组患者提高(P<0.05);B组患者治疗期间乏力、肾毒性、消化系统和骨髓抑制等不良反应发生率均明显低于A组(P<0.05)。结论与三维适行放疗与司莫司汀化疗相比,三维适行放疗与替莫唑胺化疗更有助于提高恶性胶质瘤术后患者近远期疗效以及减少不良反应发生率。     

3-O-Acetyl-11-keto-β-boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma

Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%–15% of all brain tumors. 3-O-Acetyl-11-keto-β-boswellic acid (AKBA), one of the most active ingredients of gum resin from Boswellia carteri Birdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. However, whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear. An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA. The effects of AKBA on tumor growth were evaluated using MRI. The effects on the alteration of metabolic landscape were detected by MALDI-MSI. The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence, respectively. Transmission electron microscope was used to check morphology of cells treated by AKBA. Our results showed that AKBA (100 mg/kg) significantly inhibited the growth of orthotopic U87-MG gliomas. Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma, while immunoblot assays revealed that AKBA suppressed the expression of ATG5, p62, LC3B, p-ERK/ERK, and P53, and increased the ratio of p-mTOR/mTOR. Taken together, these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy. AKBA could be a promising chemotherapy drug for glioblastoma.     

Pharmacokinetics,safety, and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial

BackgroundThe poly(ADP-ribose) polymerase (PARP) inhibitor olaparib potentiated radiation and temozolomide (TMZ) chemotherapy in preclinical glioblastoma models but brain penetration was poor. Clinically, PARP inhibitors exacerbate the hematological side effects of TMZ. The OPARATIC trial was conducted to measure penetration of recurrent glioblastoma by olaparib and assess the safety and tolerability of its combination with TMZ.MethodsPreclinical pharmacokinetic studies evaluated olaparib tissue distribution in rats and tumor-bearing mice. Adult patients with recurrent glioblastoma received various doses and schedules of olaparib and low-dose TMZ in a 3 + 3 design. Suitable patients received olaparib prior to neurosurgical resection; olaparib concentrations in plasma, tumor core and tumor margin specimens were measured by mass spectrometry. A dose expansion cohort tested tolerability and efficacy of the recommended phase II dose (RP2D). Radiosensitizing effects of olaparib were measured by clonogenic survival in glioblastoma cell lines.ResultsOlaparib was a substrate for multidrug resistance protein 1 and showed no brain penetration in rats but was detected in orthotopic glioblastoma xenografts. Clinically, olaparib was detected in 71/71 tumor core specimens (27 patients; median, 496 nM) and 21/21 tumor margin specimens (9 patients; median, 512.3 nM). Olaparib exacerbated TMZ-related hematological toxicity, necessitating intermittent dosing. RP2D was olaparib 150 mg (3 days/week) with TMZ 75 mg/m² daily for 42 days. Fourteen (36%) of 39 evaluable patients were progression free at 6 months. Olaparib radiosensitized 6 glioblastoma cell lines at clinically relevant concentrations of 100 and 500 nM.ConclusionOlaparib reliably penetrates recurrent glioblastoma at radiosensitizing concentrations, supporting further clinical development and highlighting the need for better preclinical models.     

替莫唑胺与尼莫司汀在脑恶性胶质瘤化疗中的疗效对比研究

目的:观察对比替莫唑胺与尼莫司汀在恶性胶质瘤(WHOⅢ,Ⅳ)的疗效.方法:120例恶性胶质瘤患者随机分为替莫唑胺治疗组及尼莫司汀对照组,治疗至少4个疗程,观察有效率、无进展生存时间、总生存时间及不良反应.结果:替莫唑胺较尼莫司汀有更高的有效率,生存时间长,不良反应较小.结论:替莫唑胺治疗恶性胶质瘤比尼莫司汀更有优势.     

替莫唑胺在恶性胶质瘤综合治疗中的临床疗效观察

目的探讨替莫唑胺(TMZ)在恶性胶质瘤综合治疗中的有效性和安全性。方法对63例恶性脑胶质瘤患者资料进行回顾性分析,其中19例接受手术+TMZ化疗的综合性治疗;21例接受手术+外放疗的综合性治疗;23例接受手术+外放疗+TMZ化疗的综合性治疗。观察各组生存率、无进展生存时间、总生存时间和TMZ药物安全性。结果手术+外放疗+TMZ化疗组的年生存率明显高于其他组。3组的平均无进展生存时间为依次为(41.5±3.95),(45.72±3.74),(56.33±3.36)周;平均总生存时间依次为(47.65±3.97),(56.33±3.74),(62.27±3.19)周。有2个病人使用TMZ出现白细胞减少,经减量处理后好转。结论替莫唑胺结合手术和外放疗是恶性胶质瘤的有效治疗方法,病人可良好耐受。