替莫唑胺联合放射治疗复发性恶性脑胶质瘤的临床疗效

目的探讨替莫唑胺联合放射治疗复发性恶性脑胶质瘤的临床疗效。方法选取52例复发性恶性脑胶质瘤患者为研究对象,随机将患者分为对照组和实验组,每组26例,给予对照组患者三维适形放射治疗,实验组在对照组的基础上给予口服150 mg/(m^2·d)替莫唑胺治疗,分析比较2组患者的临床疗效及不良反应,并对2组患者进行为期1年的随访,记录患者生存状态。结果实验组患者临床治疗有效率为73.08%,明显高于对照组的46.15%(P<0.05)。治疗后实验组患者的卡氏评分及生活质量改善率明显高于对照组(P<0.05)。2组临床均未见治疗性死亡患者,主要临床不良反应表现为中轻度白细胞计数减少、放射性脑水肿、恶心呕吐、发热、骨髓抑制及贫血等症状(P>0.05)。实验组患者1年随访生存率为92.31%,明显高于对照组的84.62%;复发率(3.85%)明显低于对照组的15.38%(P<0.05)。结论替莫唑胺联合放射治疗是复发性恶性脑胶质瘤较为理想的治疗方式,对于改善患者生活质量、提高患者生存率有积极作用,值得临床推广应用。     

放化疗同步与单纯放疗治疗胶质母细胞瘤的疗效比较

目的 比较单纯放疗(RT)与放疗加替莫唑胺(RT-TMZ)治疗胶质母细胞瘤的局控率、生存率及不良反应.方法 对60例首次术后的胶质母细胞瘤随机分为接受单纯放疗、放疗加每天持续的替莫唑胺治疗以及6个周期的替莫唑胺辅助治疗.每组30例.主要研究目标为整体生存率.结果 RT-TMZ组与RT组总有效率分别为53.3%和26.6%;1年累计局部复发率分别为63.3%和90.0%,1年无复发生存率分别为36.7%和10.0%,1年生存率分别为56.7%和16.7%(P<0.05).RT-TMZ组常见不良反应是恶心,呕吐,白细胞和血小板下降,但仅限于Ⅰ～Ⅱ度.结论 在提高局控率、延缓肿瘤复发与提高患者无瘤生存期方面RT-TMZ组要优于RT组,而不良反应方面两组反应均较轻微.     

Temozolomide in malignant gliomas: current use and future targets

Temozolomide (TMZ) is an oral alkylating agent that is regarded as a tolerable and effective drug. When combined with radiotherapy in patients with newly diagnosed glioblastoma, survival is significantly prolonged. This finding has led to widespread use of TMZ for patients with this disease. We summarize developing concerns regarding the use of TMZ, imaging of malignant gliomas, and the pharmacology of TMZ—mechanism of action, scheduling and strategies for overcoming resistance.     

Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide

Purpose: Despite the progress made in neurosurgery and radiotherapy, the prognosis of glioblastoma multiforme (GB) is poor, due to the lack of an effective salvage therapy. In vitro analysis revealed activity for ifosfamide and temozolomide. The usefulness of these agents in recurrent disease was investigated. Methods: Six adult patients with recurrent GB received one to four courses of 1,500 mg/m² ifosfamide given over 5 days intravenously. Furthermore, temozolomide (100–200 mg/m²) was given orally over 5 days to 14 patients. Results: After ifosfamide treatment, one partial response and two cases of stable disease were observed. The median survival time was 24 weeks (range of 9–52 weeks). Toxicity analysis revealed one paranoid reaction, three grade III leukocytopenia, and one grade I–II nausea, anemia, and hematuria. Temozolomide therapy resulted in three partial responses and four cases of stable disease. The median survival time (Kaplan-Meier) was 21 weeks (range 4–64 weeks). The major toxicities were grade I–II nausea and hematological side effects (one case of grade IV leuko- and thrombocytopenia). Conclusions: Ifosfamide treatment might be a feasible approach, but it necessitates hospitalization. Temozolomide showed promising results. Due to its oral application, the patient's quality of life (time out of hospital) is favorable. Subgroups with improved survival were observed. Received: 7 December 1998 / Accepted: 21 January 1999     

Prediction of Response to Concurrent Chemoradiotherapy with Temozolomide in Glioblastoma: Application of Immediate Post-Operative Dynamic Susceptibility Contrast and Diffusion-Weighted MR Imaging

ObjectiveTo determine whether histogram values of the normalized apparent diffusion coefficient (nADC) and normalized cerebral blood volume (nCBV) maps obtained in contrast-enhancing lesions detected on immediate post-operative MR imaging can be used to predict the patient response to concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ).ResultsThe 99th percentile of the cumulative nCBV histogram (nCBV C99) on immediate post-operative MR imaging was a significant predictor of one-year progression (p = 0.033). ROC analysis showed that the best cutoff value for predicting progression after CCRT was 5.537 (sensitivity and specificity were 72.7% and 76.9%, respectively). The patients with an nCBV C99 of < 5.537 had a significantly longer PFS than those with an nCBV C99 of ≥ 5.537 (p = 0.026).ConclusionThe nCBV C99 from the cumulative histogram analysis of the nCBV from immediate post-operative MR imaging may be feasible for predicting glioblastoma response to CCRT with TMZ.     

Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy – Results of a United Kingdom phase II trial (CNS 2007 04)

Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28 d) of temozolomide was studied with the aim of overcoming O⁶-methylguanine methyltransferase (MGMT) mediated resistance.Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75 mg/m²) after which up to 12 courses of 21 d of adjuvant temozolomide (75–100 mg/m²) were given 4 weekly. The trial used a 2-stage design and passed interim analysis.At diagnosis median age was 8 years (2–20 years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10–100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9 months, 35% (21%, 49%) at 1 year and 17% (7%, 30%) at 2 years. Median survival was 9.5 months (range 7.5–11.4 months). There were five 2-year survivors with a median age of 13.6 years at diagnosis.This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration.