PARP抑制剂与替莫唑胺在MGMT高表达的肺癌脑转移中有协同作用

PARP Inhibitor and Temozolomide are Synergy in MGMT High Expressed in Non-samll Cell Lung Carcinoma

非小细胞肺癌脑转移的患者在临床十分常见,患者的预后情况都较差。然而烷化剂替莫唑胺和PARP抑制剂Veliparib在这一疾病中的应用至今都没有文献报道。为了提高该类患者的预后效果,我们利用定量PCR的方法筛选了MGMT高表达的非小细胞肺癌脑转移患者57例。我们针对这一分子表型的患者随机分成3组,分别用安慰剂、替莫唑胺和联合替莫唑胺与Veliparib进行治疗,并观察后期生存情况。用安慰剂一组的患者的中位生存期只有75 d,而单独使用替莫唑胺治疗的一组患者中位生存期为82 d。与安慰剂组相比,联合替莫唑胺和Veliparib用药组患者中位生存期显著增加了46 d(p=0.028),其中位生存期为121 d。总的来说,我们用MGMT基因对非小细胞脑癌患者做了进一步的细分,并开创性地使用替莫唑胺和Veliparib联合应用对其治疗,疗效显著,为非小细胞肺癌脑转移的治疗提供切实可行临床依据。

Patients with brain metastasis of non-small cell lung carcinoma are common in the clinical, and the bad prognosis is universally acknowledged. While the combination therapic effect of alkylating agent temozolomide and PARP inhibitor Veliparib in this disease are still poorly understood. To elevate the curative effect, we screened out 57 patients with MGMT high expression from 146 patients suffered from non-small cell lung cancer and with brain metastasis. Further these patients separated into three groups, and treated with placebo, or temozolomide, or combination of temozolomide and veliparid respectively. Prognosis observation showed that the median survival is only 75 days in the placebo group, while the patients treated with temozolomide lived longer. Its median survival is 82 days. Surprisingly, compared to the placebo, the patient treated with temozolomide and veliparib had a better clinical prognosis. Its median survival is 121 days, which increased 46 days compared to the placebo （p =0.028）. Taken together, in this research we classify the non-small cell lung cancer by MGMT expression level, and creatively therapy this disease with temozolomide and veliparib, and the prognosis is favorable. Finally we provided an operable therapy method for non-small cell lung carcinoma with brain metastasis.