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替莫唑胺治疗新诊断的间变性少突胶质细胞瘤:一项临床疗效试验。

Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial.

作者信息

Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T

机构信息

Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Hebrew University Hospital, Ein-Kerem, Jerusalem, Israel.

出版信息

J Neurooncol. 2006 Sep;79(2):153-7. doi: 10.1007/s11060-005-9020-1. Epub 2006 Jul 20.

Abstract

PURPOSE

Chemotherapy with alkylating agents is of proven efficacy in recurrent anaplastic oligodendroglioma (AO) with reported response rates ranging between 50% and 70%. The response of newly diagnosed AO to initial treatment with temozolomide (TMZ) has not yet been reported. This study evaluated the response and time to tumor progression of newly diagnosed AO initially treated with TMZ.

PATIENTS AND METHODS

Twenty patients with a median age of 47 (range: 26-65) received a median of 14 (range: 3-24) cycles of TMZ as their first modality of therapy following diagnosis of AO. Treatment was given every 28 days for 5 days at a starting dose of 200 mg/m2/d and was continued for 24 cycles unless toxicity or tumor progression required withdrawal of TMZ. MRI evaluations were repeated every 8 weeks and scales of Karnofsky performance status (KPS) and of neurological function were used to assess clinical response.

RESULTS

Clinical improvement was observed in 60% of the patients with statistically significant gain measured by KPS and the neurologic function scales. The objective response rate was 75%, and median time to tumor progression was 24 months. Maximal objective response was reached within a median of 6 months (range: 3-12). Tumors with 1p loss had longer progression free survival compared to tumors without deletions (PFS at 24 months: 1p LOH = 100%, 1p intact = 20%; P = 0.057). TMZ was well tolerated with only two events of grade 3/4 hematological toxicity.

CONCLUSIONS

Newly diagnosed AO demonstrates a high rate of response to initial therapy with TMZ, similar to the response reported for PCV combination therapy. Further studies are needed to determine the optimal duration of treatment and whether radiotherapy should immediately follow chemotherapy.

摘要

目的

烷化剂化疗对复发性间变性少突胶质细胞瘤(AO)疗效已获证实,报道的缓解率在50%至70%之间。新诊断的AO对替莫唑胺(TMZ)初始治疗的反应尚未见报道。本研究评估了新诊断为AO且初始接受TMZ治疗的患者的反应及肿瘤进展时间。

患者与方法

20例患者,中位年龄47岁(范围:26 - 65岁),在诊断AO后接受中位14个周期(范围:3 - 24个周期)的TMZ作为其首个治疗方案。每28天给药5天,起始剂量为2mg/m²/d,持续24个周期,除非毒性或肿瘤进展需要停用TMZ。每8周重复进行MRI评估,并使用卡诺夫斯基功能状态(KPS)量表和神经功能量表评估临床反应。

结果

60%的患者观察到临床改善,通过KPS和神经功能量表测量有统计学意义的改善。客观缓解率为75%,中位肿瘤进展时间为24个月。中位6个月(范围:3 - 12个月)内达到最大客观缓解。与无缺失的肿瘤相比,有1p缺失的肿瘤无进展生存期更长(24个月时的无进展生存期:1p杂合性缺失 = 100%,1p完整 = 20%;P = 0.057)。TMZ耐受性良好,仅发生两例3/4级血液学毒性事件。

结论

新诊断的AO对TMZ初始治疗显示出高缓解率,类似于PCV联合治疗报道的缓解率。需要进一步研究以确定最佳治疗持续时间以及放疗是否应在化疗后立即进行。

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