不同化疗方案治疗放疗后进展的小细胞肺癌脑转移患者效果及安全性比较

Comparison of efficacy and safety of different chemotherapy regimens for progressive patients with brain metastasis of small cell lung cancer after radiotherapy

目的 分析不同化疗方案对放疗后进展的小细胞肺癌脑转移患者的治疗效果及耐受性.方法 回顾性分析96例小细胞肺癌脑转移全脑放疗后颅内病灶进展患者,分为卡莫司汀组（28例）、替莫唑胺组（19例）、拓扑替康组（24例）、未化疗组（25例）.结果 就脑内转移灶而言,全组无完全缓解病例,卡莫司汀组部分缓解（PR）率、疾病稳定（SD）率、疾病进展（PD）率分别为17.8%（5/28）、53.6%（15/28）、28.6%（8/28）,颅内病灶治疗有效率（RR）为17.9%（5/28）,疾病控制（CR＋PR＋SD）率为71.4%（20/28）.替莫唑胺组PR、SD、PD率分别为15.8%（3/19）、63.2%（12/19）、21.1%（4/19）,颅内病灶RR为15.8%（3/19）,疾病控制率为78.9%（15/19）.拓扑替康组PR、SD、PD率分别为8.3%（2/24）、54.2%（13/24）、37.5%（9/24）,颅内病灶RR为8.3%（2/24）,疾病控制率为62.5%（15/24）.未化疗组无缓解患者,20例（80.0%）颅内病灶进展.卡莫司汀组、替莫唑胺组、拓扑替康组、未化疗组中位无进展生存（PFS）期分别为（3.64±0.43）、（4.68±0.49）、（3.58±0.50）、（2.60±0.31）个月,中位生存（OS）期分别为（18.80±1.74）、（18.76±1.85）、（19.10±1.64）、（9.64±0.84）个月,三个化疗药物治疗组与未化疗组OS比较,差异有统计学意义（P=0.002）.四组Ⅲ~Ⅳ级血液学毒性相似,替莫唑胺组胃肠道反应及乏力发生率低,未化疗组乏力及头痛等中枢神经系统症状较多.结论 小细胞肺癌脑转移放疗后进展的患者化疗后可提高近期缓解率,延长OS,PFS无明显延长.卡莫司汀、替莫唑胺、拓扑替康化疗患者近期及远期疗效相近,替莫唑胺不良反应小,疾病控制率高,积极应用能透过血脑屏障的化疗可提高小细胞肺癌脑转移放疗后进展患者的治疗效果,且耐受性良好.

Objective To analyze the efficacy and safety of different chemotherapy regimens for treatment of progressive patients with small cell lung cancer （SCLC） brain metastasis after radiotherapy. Methods 96 SCLC brain metastasis patients with progressive intracranial lesions after radiotherapy were divided into four groups： carmustine group （Group A, 28 cases）, temozolomide group （Group B, 19 cases）, topotecan group （Group C, 24 cases） and no chemotherapy group （Group D, 25 cases）. Results In terms of brain metastases, there were no complete response cases in the whole groups. The rates of partial remission （PR）, stable disease （SD） and progression of disease （PD） in Group A were 17.8%（5/28）, 53.6%（15/28） and 28.6 % （8/28）, respectively, the response rate （RR） of intracranial lesions was 17.9 % （5/28）, and disease control （CR＋PR＋SD） rate was 71.4%（20/28）. The rates of PR, SD and PD in Group B were 15.8%（3/19）, 63.2 % （12/19） and 21.1 % （4/19）, respectively, the RR of intracranial lesions was 15.8 % （3/19）, and disease control rate was 78.9 % （15/19）. The rates of PR, SD and PD in Group D were 8.3 % （2/24）, 54.2 %（13/24） and 37.5 % （9/24）, respectively, the RR rate of intracranial lesions was 8.3 % （2/24）, and disease control rate was 62.5 % （15/24）. In Group D, there was no response case, and 20 patients with PD （80.0 %） were found. The median progression-free survivals （PFSs） were （3.64 ±0.43） months, （4.68 ±0.49） months,（3.58 ±0.50） months, （2.60 ±0.31） months in Group A, B, C and D, respectively, and the median overall survivals （OSs） were （18.80±1.74） months, （18.76±1.85） months, （19.10±1.64） months and （9.64±0.84） months, respectively. The median OS of Group A, B or C was longer than that of Group D （P=0.002）. The differences of grade Ⅲ-Ⅳhematologic toxicities among the four subgroups were not statistically different. Patients in Group B had better tolerance to nausea and vomit. In Group D, the central nervous system symptoms such as fatigue and headache occurred frequently. Conclusions The response rate and OS of SCLC brain metastasis patients with progressive intracranial lesions after radiotherapy are improved after chemotherapy, however, PFS is not significantly prolonged. The efficacies of carmustine, temozolomide and topotecan are similar in short and long term, besides, temozolomide shows less adverse events and a higher disease control rate. The application of chemotherapy that could penetrate the blood-brain barrier can improve the efficacy on SCLC brain metastasis patients with progressive intracranial lesions after radiotherapy with well tolerance.