替莫唑胺联合放射治疗治疗恶性脑胶质瘤的疗效观察

目的探讨替莫唑胺(TMZ)联合放射治疗治疗恶性脑胶质瘤的临床疗效和安全性评价。方法收集56例病理学诊断为恶性脑胶质瘤的患者,其中III级患者为32例,IV级患者为24例。根据不同的治疗方法将患者分为TMZ联合放疗(TMZ-RT)组(30例)和单纯放疗(RT)组(26例)。TMZ-RT组患者采用放疗联合TMZ化疗(75 mg·m-2·d-1)治疗6周,放疗后继续给予TMZ序贯/辅助(150²00 mg·m-2·d-1)化疗2200 mg·m-2·d-1)化疗2⁴周。RT组患者接受立体定向适形放射治疗1.84周。RT组患者接受立体定向适形放射治疗1.8³Gy/d,部分患者接受超分割放射治疗,总剂量为603Gy/d,部分患者接受超分割放射治疗,总剂量为60⁷5 Gy。治疗结束后评估两组患者的生存率和近期疗效。结果影像学结果显示,TMZ-RT组完全缓解8例,部分缓解9例,稳定10例,进展3例;RT组完全缓解6例,部分缓解8例,稳定8例,进展4例,两组差异无统计学意义(P>0.05)。TMZ-RT组患者的1、2、3年生存率分别为86.7%、80.0%和56.7%。RT组患者的1、2、3年生存率分别为73.1%、30.8%和11.5%,两组患者的2年和3年生存率比较,差异有统计学意义(P<0.05)。TMZRT组和RT组患者的中位复发时间分别为(23.1±8.7)个月和(15.8±8.9)个月,两组差异有统计学意义(P<0.05)。TMZ-RT组和RT组患者化疗后KPS评分别为(89.8±9.7)分和(65.4±10.3)分,两组间差异有统计学意义(P<0.05)。TMZ-RT组患者的不良反应发生率较低且,患者的生活质量水平显著高于RT组患者(P<0.05)。结论 TMZ联合放疗与单纯放疗治疗恶性脑胶质瘤的近期疗效相当,但TMZ联合放疗能够显著提高2年和3年的生存率并延缓复发时间。TMZ联合放疗治疗不良反应轻,安全性高,能够改善患者的生活质量,值得临床进一步推广。     

Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients

Objective

This study was performed to determine the safety and outcome of concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide for Korean patients with a newly diagnosed glioblastoma.

Methods

Patients were recruited from four institutions between 2004 and 2007. The patients received fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks and daily temozolomide, followed by 6 cycles of adjuvant temozolomide. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response, and safety.

Results

A total of 103 patients were enrolled in this study. Ninety-six patients (93%) completed the CCRT and 54 patients (52%) received 6 cycles of adjuvant temozolomide. The response rate was 73% (53/73) and the tumor control rate was 92% (67/73). Of the 96 patients who completed the CCRT, the median OS was 18.0 months and the 1- and 2-year OS rates were 74 and 38%, respectively. The median PFS was 10.0 months and the 1- and 2-year PFS rates were 33 and 16%, respectively. The only significant prognostic factor of survival was the extent of surgical resection (p<0.05). CCRT resulted in grade 3 or 4 hematologic toxic effects in 8% of patients. No opportunistic infections were noted.

Conclusion

This study is the first prospective multi-institutional report of CCRT and adjuvant chemotherapy with temozolomide for patients with a newly diagnosed glioblastoma in Korea. The current protocol may prolong the survival of Korean patients with a glioblastoma and may be tolerable in terms of toxicity.     

ACNU-based chemotherapy for recurrent glioma in the temozolomide era

No standard of care for patients with recurrent glioblastoma has been defined since temozolomide has become the treatment of choice for patients with newly diagnosed glioblastoma. This has renewed interest in the use of nitrosourea-based regimens for patients with progressive or recurrent disease. The most commonly used regimens are carmustine (BCNU) monotherapy or lomustine (CCNU) combined with procarbazine and vincristine (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n = 14) or in combination with other agents (n = 18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide.     

Temozolomide treatment does not affect topiramate and oxcarbazepine plasma concentrations in chronically treated patients with brain tumor-related epilepsy

Objective Medical management of brain tumor-related epilepsy is complicated by interactions between antiepileptic and chemotherapeutic drugs. We studied the effect of temozolomide therapy on the disposition of the new antiepileptic drugs topiramate (TPM) or oxcarbazepine (OXC). Methods Fifteen patients chronically treated with TPM or OXC in monotherapy starting a chemotherapeutic treatment with temozolomide were enrolled in the study, of which ten were available for the final analyses. Blood samples were collected before temozolomide treatment (T₀), at its end (T₇) and after further 1–3 weeks (T₁₄–T₂₈). For each patient, more than one treatment cycle was studied. Topiramate and OXC mono-10-hydroxy derivative (MHD) plasma concentrations were determined by hplc coupled with ion spray mass spectrometer (TPM) or ultraviolet (MHD) detection. Results Mean TPM concentrations were 5.4 ± 2.4 μg/ml at T₀ vs. 5.5 ± 2.4 μg/ml at T₇ (n = 14), and 5.4 ± 2.4 μg/ml at T₀ vs. 5.6 ± 2.8 μg/ml at T₁₄–T₂₈ (n = 14). Mean MHD concentrations were 16.4 ± 7.6 μg at T₀ vs. 18.5 ± 9.0 μg/ml at T₇ (n = 5), and 16.8 ± 7.0 μg/ml at T₀ vs. 18.0 ± 8.7 μg/ml at T₁₄–T₂₈ (n = 8) (all comparisons not statistically significant; Student’s t-test for paired samples). Conclusion Temozolomide treatment did not affect TPM plasma concentrations in chronically treated patients. Data for MHD in OXC-treated patients were similar, but, due to the small sample size, results should be interpreted cautiously.These findings confirm that TPM (and possibly OXC) are a reasonable choice of antiepileptic drug in patients with brain tumor-related epilepsy.     

A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases

Purpose To investigate the efficacy and safety of the combination of vinorelbine and intensive temozolomide for recurrent or progressive brain metastases from solid tumors. Methods Patients ≥18 years of age and with Karnofsky performance scale (KPS) ≥ 60, adequate organ function and progressive or recurrent brain metastases were eligible. This was a phase II trial with 28-day cycles using temozolomide (150 mg/m², days 1–7 and 15–21) and vinorelbine 25 or 30 mg/m² on days one and eight. The primary endpoint was objective radiographic response. Results Thirty-eight patients (15 men, 23 women) with a median age of 57 years (range, 39–75) and median KPS of 80 were enrolled. The primary tumor sites were lung (n = 20), breast (n = 11), colorectal (n = 2), kidney (n = 2), bladder (n = 1), endometrium (n = 1), head and neck (n = 1). Prior therapies included chemotherapy (97%), whole-brain radiation therapy (79%), brain metastasis resection (53%) and stereotatic radiosurgery (47%). Objective radiographic response rate was 5% (one complete response and one minor response); five patients had stable disease, 29 progressive disease and two patients were not evaluable. Twenty-nine patients (76%) have died and the median follow-up of survivors was six months. Median progression-free and overall survivals were 1.9 and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and two patients discontinued the study due to myelosuppression. Conclusions In this heavily pretreated population of patients with brain metastases, adding vinorelbine and increasing the intensity of temozolomide do not improve response rates compared to previous studies with single-agent temozolomide at standard doses.     

恶性脑胶质瘤同步放化疗中替莫唑胺化疗的不良反应及对策

目的替莫唑胺是一种新型烷化剂,因其口服给药、生物利用度好、良好的血脑屏障通透性以及突出的治疗效果,已成为恶性脑胶质瘤治疗的常规用药。本文旨在通过对替莫唑胺的不良反应的研究,以期最大限度地减轻药物的不良反应,提高患者的生存质量。方法根据2009年美国卫生与公共服务部制定的药物常见不良事件评价标准第四版(CTCAE-V4.0),观察使用替莫唑胺联合放射治疗的同步放化疗和化学治疗患者所出现的化疗不良反应,并采取积极的防治措施进行处理。结果本组95例接受替莫唑胺联合同步放化治疗的患者中,严格依据CTCAE-V4.0评价原则,得出结果如下:有20例患者出现胃肠道不良反应,其中1级的有12例,2级有8例。发生1级中性粒细胞减少的为6例,2级的为3例;1级血小板减少者3例,2级的为1例。发生脱发者为53例,1级的有41例,2级有12例。发生皮疹、斑丘疹共7例,1级的为6例,2级的为1例。所有上诉不良反应较轻,标准均为1-2级,无3、4、5级不良反应发生。在给予对症、停药处理后均能明显缓解。结论替莫唑胺是目前胶质瘤治疗的常用药物,通过对替莫唑胺联合放射治疗过程中的不良反应,显示其不良反应较轻微,且给予对症处理后均能明显缓解。因此,在对恶性脑胶质瘤患者使用同步放射治疗化学治疗中,替莫唑胺的应用是安全的。     

PDCA护理对恶性脑胶质瘤术后放疗联合替莫唑胺同期化疗所致不良反应患者生活质量的影响

目的：探讨PDCA护理对恶性脑胶质瘤术后放疗联合替莫唑胺同期化疗所致不良反应患者生活质量的影响。方法选取2011年10月-2013年10月沈阳军区总医院恶性脑胶质瘤术后放疗联合替莫唑胺同期化疗所致不良反应的患者28例,按随机数字法分为观察组与对照组,各14例,观察组给予PDCA护理,对照组给予一般常规护理,比较两组患者经护理后不良反应发生情况及生存质量评分。结果经过护理干预后,观察组恶性、呕吐等胃肠道反应占28.6%,骨髓抑制占7.2%,血液系统反应占14.3%,发生情况好于对照组（57.1%、21.4%、35.7%）,差异均有统计学意义（均P〈0.05）。经过护理干预,观察组生存质量评分包括躯体功能、角色状态、社会功能、心理健康、疼痛、精力、体力[（71.3±6.0）、（78.1±6.4）、（68.6±6.5）、（80.2±7.3）、（76.5±5.5）、（78.8±6.7）、（68.1±6.5）分]高于对照组躯体功能、角色状态、社会功能、心理健康、疼痛、精力、体力等生存质量评分[（63.2±5.5）、（69.8±6.2）、（60.3±6.2）、（73.1±7.0）、（65.7±5.4）、（67.4±6.2）、（57.9±6.3）分],差异均有统计学意义（均P〈0.05）。结论对恶性脑胶质瘤术后放疗联合替莫唑胺同期化疗所致不良反应的患者给予PDCA程序护理,可显著减少不良反应发生率,提高患者的生活质量。