贝伐单抗联合化疗治疗复发性恶性胶质瘤:附12例经验

Bevacizumab combined with chemotherapy for patients with recurrent malignant gliomas:experiences of 12 cases

背景与目的：美国综合癌症隈NationalComprehensiveCancerNet，NCCN）治疗指南推荐贝伐单抗联合化疗治疗复发性恶性胶质瘤。但截至目前，中国脑胶质瘤患者这方面的报道较少。本文总结我们应用贝伐单抗联合化疗治疗12例复发性恶性胶质瘤的临床经验，探讨安全性与疗效。方法：12例复发性恶性胶质瘤均行贝伐单抗联合化疗。贝伐单抗5mg／kg，每两周一次。TMZ化疗方案的选择基于肿瘤组织DNA甲基转移酶0^6methylguanine—DNAmethyltransferase，MGMT）的免疫组化检测结果，行甲基化特异PCRMSP—PCR）检测MGMT启动子甲基化程度。MGMT阴性表达（-）者，接受TMZ标准化疗[200mg（m2·d），d1-5，四周方案]；MGMT阳性表边＋）者，或者MGMT阴性表达（-）者既往已接受标准剂量TMZ治疗但病情进展者，接受TMZ剂量密度方案[75mg（m2·d），d1-21四周方案]。结果：12例患者共接受63次贝伐单抗治疗，中位4次3—10次）。12例患者均可评价客观疗效，完全缓解completeremission，CR）2例16．7％），部分缓鲰partialremission，PR）2例16．7％），微效minimalremission，MR）8例66．7％），疾病控制取CR＋PR＋MR）为100％。中位无进展生称progressionfreesurvival，PFS）为4．3个月（95％CI：2．4—7．3），6个月的PFS率为40．6％。最严重不良反应是Ⅲ度粒细胞减少症与白细胞减少症，各1例次1．6％）。最常见的轻至中度不良反应包括Ⅱ度的腹泻8例次12．7％）、Ⅱ度疲乏5例次7．9％）、高血压2例次3．2％）。结论：贝伐单抗联合化疗治疗国人复发恶性胶质瘤是安全的，疗效也令人满意．

BACKGROUND ＆ OBJECTIVE： Bevaeizumab, a monoclonal antibody against vascular endothehal growth factor （VEGF）, has become the standard ofcare for recurrent glioblastoma. Recent clinical trials showed that patients with malinant gliomas could benefit from bevacizumab treatment. This article was to evaluate the efficiency and side effects of bevacizumab in combined with chemo-therapy for malignant gliomas. METHODS： Patients eceived 5mg/Kg of bevacizumab infusion intravenously every 2 weeks until unacceptable toxicity or tumor progression occurred. The personalized regimen of temozolomide （TMZ） chemotherapy was selected based on MGMT expression of the tumor. Patients with MGMT-negative tumors （-） had received the standard dosing regimen （200 rag/m2 for 5 days every 28 days）. While, patients with MGMT-positive tumors （＋）, or resistant to the standard dosing regimen of TMZ, were treated with TMZ 75 mg/m2 day 1-21）using the 3-weeks-on/i-week-off （2l of 28 days） schedule. RESULTS： Twelve patients received a total of 63 times of bevacizumab ranging from 3 to 10 （median 4 times）. Complete remission （CR）, partial remission （PR） and minimal remission （MR） were found in 2 patient（ 16.7%）, 2 patient（ 16.7%）and 8 patient（66.7%）. Disease control rate（ CR ＋PR＋ MR）was 100%. The median progression free survival （PFS） was 4.3 months （ 95% CI：2.4-7.3） and PFS at 6 months was 40.6%. As to the side effects, myelosuppression including neutropenia and leukopenia were the most common high grade toxicities （grade 3）, both occurring in 1.6 % （1/63） of patients. The most frequent toxicities were diarrhea （grade 2） （12.7%）, fatigue （grade 2） （7.9%）, and hypertension （3.2%）. CONCLUSION： Bevacizumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and toxicities were well tolerable.