血清VEGF对塞来昔布治疗晚期肺癌的预测作用

Predictive value of serum VEGF in patients with advanced non-small cell lung cancer treated with vinorelbine

目的验证以下假设:治疗开始前的低水平血清VEGF预示存活时间较长,而环氧合酶-2(COX-2)抑制剂塞来昔布联合化疗能提高非小细胞肺癌(NSCLC)的缓解率和生存期。方法本试验为双盲单中心III期试验,选取81例IIIB或IV期NSCLC患者,ECOG体力状态评分为0-2入组。随机给予塞来昔布或安慰剂400 mg b.i.d联合4周期长春瑞滨/铂类化疗。塞来昔布计划给药时间最长1年,如疾病进展或出现严重毒性可停药。在治疗起始和4周期化疗结束后,检测所有患者血清VEGF水平。结果 81例患者治疗起始的VEGF水平中位值是340.98pg/m L。4周期化疗结束后VEGF平均值下降。总体生存期(OS)塞来昔布组vs安慰剂组为17.5月vs15.9月(P=0.837);无进展生存期(PFS)塞来昔布组vs安慰剂组为14.4月vs 7月(P=0.000)。治疗起始的VEGF水平≥340.98pg/m L组患者OS较VEGF水平<340.98pg/m L组差(13.2月vs 26月,P=0.000),PFS也缩短(3.5月vs8.5月,P=0.000)。结论治疗前血清VEGF低水平能预示塞来昔布对生存期的正效应。

Objective To investigate the predictive value of serum VEGF in patients with advanced non-small cell lung cancer treated with vinorelbine. Methods A study was performed in patients with stage IIIb/IV NSCLC who had pathologic confirmation, no prior chemotherapy, Eastern Cooperative Oncology Group （ ECOG） per-formance status of 0 to 2, and adequate organ function. Treatment consisted of vinorelbine and cisplatin/carboplatin every 4 weeks for four cycles. Patients were randomly assigned to receive celecoxib 400 mg or placebo twice daily. Primary end point was overall survival （ OS） . Serum VEGF levels of all patients were detected at onset and endpoint of treatment. Results The median value of VEGF was 340. 98pg/ml before treatment. The mean value of VEGF de-creased after 4 cycles chemotherapy. The overall survival （ OS） of the celecoxib group was 17. 5m, longer than 15. 9m of the control group （P=0. 837）. The progression free survival （PFS） of the celecoxib group was 14. 4m, longer than 7m of the control group （P=0. 000）. OS of patients with high serum VEGF level （≥340. 98pg/mL） be-fore treatment was shorter than low VEGF level （ 〈340. 98pg/mL） （13. 2m vs 26m, P=0. 000）. PFS was also poo-rer in the high VEGF group （3. 5m vs 8. 5m, P=0. 000）. Conclusion In patients with advanced NSCLC, celecox-ib can not improve survival significantly. Low pre-treatment serum level of VEGF appears to be predictive of a posi-tive effect of celecoxib on survival.