卡铂联合替莫唑胺剂量密度方案治疗复发性胶质母细胞瘤的临床观察

Clinical observation of carboplatin in combination with temozolomide dose-dense regimen for recurrent glioblastoma

目的观察卡铂联合替莫唑胺（TMZ）剂量密度方案治疗复发性胶质母细胞瘤（GBM）的有效性、耐受性及安全性。方法纳入2013年2月至2014年3月吉林大学第一医院放疗科的9例成人复发性GBM患者，均采用卡铂联合TMZ剂量密度方案治疗。具体方案：卡铂350mg／m2，第1天；TMZ 150mg·m-2·d-1，第1—7天，第15—21天，28d为1个周期。随访时间为5～16个月。结果7例患者行4个周期化疗；2例行5个周期化疗。主要毒性反应为血液学毒性反应、消化道反应及乏力。3例发生Ⅰ～Ⅱ度骨髓抑制；6例出现Ⅲ～Ⅳ度骨髓抑制。所有患者均有厌食、呕吐等轻、中度消化道反应。以上不良反应经对症治疗后缓解；无一例发生治疗相关性死亡。5例患者死于肿瘤进展；6个月无进展生存率为44％（4／9）；影像学缓解率为44％（4／9）；症状改善率为67％（6／9）；1年生存率为22％（2／9）。结论采用卡铂联合TMZ剂量密度方案治疗复发性GBM有效；4—5个周期化疗患者多可耐受；未见严重不可逆不良反应发生。

Objective To investigate the effectiveness, tolerability and safety of carboplatin in combination with temozolomide （TMZ） dose-dense regimen for the treatment of recurrent glioblastoma （GBM）. Methods From February 2013 to March 2014, 9 adult patients with recurrent GBM received carboplatin in combination with temozolomide dose-dense regimen at the Department of Radiotherapy, the First Hospital of Jilin University were collected. The specific regimen： carboplatin 350 mg/m2 at day 1 ; TMZ 150 mg·m-2·d-1, at day 1 -7 and day 15 -21, and 28 days were acircle. The follow-up time ranged from 5 to 16 months. Results Four cycles of chemotherapy were performed in 7 patients; 5 cycles of chemotherapy were performed in 2 patients. The main toxic reactions were hematological toxic reactions, gastrointestinal reactions, and fatigue. Three patients had grade Ⅰ～Ⅱ of bone marrow suppression; 6 patients had grade Ⅲ～Ⅳ of bone marrow suppression. All patients had mild to moderate gastrointestinal reactions including anorexia and vomiting. All the above adverse reactions were alleviated after symptomatic treatment; none of them had treatment-related deaths. Five patients died of tumor progression. The progression-free survival rate of 6 months was 44% （4/9） ; the imaging remission rate （PR） was 44% （4/9）; the symptom improvement rate was 67% （6/9）; and the 1-year survival rate was 22% （2/9）. Conclusions Carboplatin in combination with TMZ dose-dense regimen for the treatment of recurrent GBM was effective. Most of the patients with 4 - 5 cycles of chemotherapy could tolerate it. No severe irreversible adverse reactions occurred.