贝伐株单抗治疗国人复发恶性胶质瘤的初步临床分析与评估

Preliminary clinical evaluations of bevacizumab for recurrent malignant glioma in Chinese patients

目的了解贝伐株单抗（BEV）治疗国人复发恶性胶质瘤（HGG）的临床疗效，评估其不良反应发生率和使用安全性。方法选取2010年1月至2013年12月在南方医科大学南方医院行BEV（10mg／kg，每2周）联合替莫唑胺（TMZ，150mg／m2，5d／28d）治疗的15例复发HGG患者，其中胶质母细胞瘤（GBM）12例，间变性星形细胞瘤（AA）3例，判断其影像学和临床获益，行无进展生存（PFS）及总体生存分析，评估不良反应出现情况及严重程度。结果使用后出现高血压2例，切口愈合不良并发颅内感染1例，恶心呕吐2例，脑脊液漏1例，经积极治疗以上不良反应均治愈。按照RANO标准，15例中，短期（〈3个月）明显影像学和临床获利的11例（73．3％），使用6个月后仍无肿瘤进展8例（53．3％），平均PFS时间（8±5）个月。长期随访（〉6个月），8例肿瘤再进展，其中5例死亡，总体生存时间（24±10）个月。结论对比西方人种，BEV化疗对国人复发HGG有更好的短期临床和影像学效果，但长期疗效无明显差异。严重不良反应发生率较西方人种低，临床耐受性良好。对再次手术患者，应推迟至术后1个月左右使用，以减少切口愈合相关并发症。

Objective To explore the clinical efficacies of bevacizumab （BEV） for high-grade glioma （HGG） in Chinese patients and evaluate its profiles of adverse events and usage safety. Methods A total of 15 HGG cases, including glioblastoma multiform （GBM） （n = 12） and anaplastic astrocytoma （AA） （n =3） , were selected to receive the treatments of BEV （10 mg/kg, q2w） and temozolomid （TMZ, 150 mg/m2, 5 d/28 d ）. Their radiological responses, clinical status, progression-free survival （PFS） and overall survival （OS） were evaluated. Also their adverse events and severity were recorded and analyzed. Results According to the RANO criteria, during the short period （ 〈 3 months）, 11 cases had significant radiological and clinical responses. However, only 4 cases responded during a follow-up period of beyond 3 months. Three cases had reprogression after BEV chemotherapy. At 6 months post-treatment, 8 cases （53.3 % ） survived without lesion progression and the median PFS was 8 ± 5 months. During a longer follow- up （ 〉 6 months ）, 8 patients had tumor reprogression, including 5 deaths. The median overall survival period was 24 ± 10 months. The adverse events included hypertension （n = 2）, wound-healing complication （ n = 1 ）, vomiting （ n = 2 ） and cerebro-spinal fluid leakage （ n = 1 ）. All complications were cured by activate supportive measures. Conclusion After BEV treatment, most patients obtain more significant short- term responses with good toleration. For re-operative cases, the usage of BEV should be deferred to one month post-operation so as to avoid the occurrence of wound-healing complications.