Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up
Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up
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DOI：
10.1631/jzus.b0820248
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发表时间：
2009-05-01
影响因子：
5.1
通讯作者：
Hu, Ying
中科院分区：
文献类型：
--
作者：
Guan, Yong-song;Liu, Yuan;Hu, Ying
本研究采用非随机、双组临床试验，观察了58例晚期非小细胞肺癌（NSCLC）患者经支气管动脉灌注（BAI）联合重组人p53抑癌基因腺病毒（rAd-p53）治疗的安全性和有效性。其中19例接受BAI和rAd-p53联合治疗（联合组），其余39例仅接受BAI治疗（对照组）。患者随访12个月，分别采用美国国家癌症研究所的常见毒性标准和实体瘤反应评价标准（RECIST）评价安全性和局部反应。采用Kaplan-Meier法比较两组患者的疾病进展时间（TTP）和生存率，联合组19例患者分别接受rAd-p53注射49次和BAI治疗46次，对照组39例患者接受BAI治疗113次。与对照组相比，联合治疗组厌食、恶心呕吐、疼痛、白细胞减少等不良反应较少（P < 0.05），关节痛、发热、流感样症状、肌痛等不良反应较多（P < 0.05）。联合组和对照组的总有效率（完全缓解（CR）+部分缓解（PR））分别为47.3%和38.4%（P > 0.05）。联合治疗组患者的TTP长于对照组（中位数7.75 vs 5.5个月，P=0.018）。然而，联合治疗并没有带来更好的生存率，联合治疗组3、6和12个月的生存率分别为94.74%、89.47%和52.63%，而联合治疗组分别为92.31%、69.23%、结果表明，rAd-p53联合BAI治疗NSCLC患者耐受性良好，可改善患者生活质量，延缓疾病进展。进一步的研究，以更好地确定这种联合治疗的疗效是必要的。
In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) injection in patients with advanced non-small-cell lung cancer (NSCLC) in the combination with the therapy of bronchial arterial infusion (BAI).A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 (the combo group), while the remaining 39 were treated with only BAI (the control group). Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer Institute's Common Toxicity Criteria and response evaluation criteria in solid tumor (RECIST), respectively. Time to progression (TTP) and survival rates were also analyzed by Kaplan-Meier method.In the combo group, 19 patients received a total of 49 injections of rAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia (P < 0.05) but more arthralgia, fever, influenza-like symptom, and myalgia (P < 0.05), compared with the control group. The overall response rates (complete response (CR)+partial response (PR)) were 47.3% and 38.4% for the combo group and the control group, respectively (P > 0.05). Patients in the combo group had a longer TTP than those in the control group (a median 7.75 vs 5.5 months, P=0.018). However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, compared with 92.31%, 69.23%, and 38.83% in the control group (P=0.224).Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the quality of life and delayed the disease progression. A further study to better determine the efficacy of this combination therapy is warranted.