重组人p53腺病毒联合治疗晚期恶性肿瘤的临床观察

目的：探讨重组人p53腺病毒注射液（rAd-p53）治疗恶性肿瘤的疗效及安全性。方法：对67例晚期无法行手术切除的恶性肿瘤患者,或术后肿瘤转移、无法再手术的患者,采用瘤内注射、血管介入和静脉滴注rAd-p53联合化疗和放疗,至少1个疗程以上,通过临床观察、KPS评分、CT或MRI检查以及随访,评价rAd-p53联合化、放疗的临床疗效。结果：67例患者治疗有效率为47.8%,疾病控制率为89.6%,其中CR患者4例,分别为卵巢癌1例,皮肤癌1例,鼻咽癌2例。rAd-p53联合放疗41例,联合化疗26例,有效率分别为56.1%和34.6%（P〈0.05）,疾病控制率分别为95.1%和80.8%（P〈0.05）。全组中位生存时间为60个月（6～117个月）;联合治疗后,全组中位生存时间为24个月（2～34个月）。不良反应主要为自限性发热,另有个别胃肠道反应及肌肉酸痛。结论：rAd-p53对多种恶性肿瘤具有一定疗效,临床应用安全;局部给药联合放疗可能比联合化疗更能提高肿瘤的局控率。

The clinical observation of effect of recombinant human Ad-p53 combined with chemotherapy or radiotherapy in advanced cancer patients

Objective：To evaluate the efficacy and toxicity of combination therapy with recombinant adenovirus-p53（rAd-p53,Gendicine） and chemotherapy or radiotherapy in advanced cancer patients.Methods：A total of 67 patients with advanced cancer have been treated with chemotherapy or radiotherapy combined with rAd-p53 by local injection（intratumoral or transcatheter） or intravenous injection.A course of treatment was weekly for four vices of injection.All patients were assessed for response and toxicity by clinical observation,computed tomography（CT） or magnetic resonance imaging（MRI） examination and follow-up.Results：The response rate（RR） was 47.8%,and the tumor control rate（TCR） was 89.6% in the treated group,in which only 4 patients achieved in CR,including one patient with ovary carcinoma,one with skin carcinoma,and two with nasopharyngeal carcinoma.There were 41 patients treated with rAd-p53 combined with radiotherapy,while 26 patients treated with rAd-p53 combined with chemotherapy.The RR and TCR of the former group was 56.1% and 95.1%,which was significantly higher than the 34.6% and 80.8% of the latter group（P〈0.05）.The overall survival time was 6 to 117 months with median 60 months,while the survival time after the combination therapy was 2 to 34 months with median 24 months.All 67 patients received multiple injections of Gendicine and neither dose-limiting toxicity nor adverse event was noted,except transient fever after Gendicine administration.Conclusion：Treatment with local or intravenous injection of rAdp53 plus chemotherapy or radiotherapy on advanced cancer is safe and effective.Local injection of rAdp53 combined with radiotherapy may be much effective to enhance the tumor local control rate than the intravenous injection of rAdp53 combined with chemotherapy.Our results imply that rAdp53 is an effective gene-therapeutic agent for treatment of advanced cancer.