重组人p53腺病毒注射液治疗晚期实体肿瘤的安全性和近期疗效评价

Safety and primary efficacy of recombinant human adenovirus-p53 injection on advanced solid tumor

目的:总结重组人p53腺病毒注射液(rAdp53)治疗的晚期实体肿瘤患者的资料,初步评价其安全性与疗效。方法:常规治疗失败的晚期实体肿瘤患者24例,其中肾癌5例,鼻咽癌4例,结直肠癌4例,黑色素瘤2例,非小细胞肺癌1例,食管癌1例,贲门癌1例,胸腺癌1例,十二指肠癌1例,甲状腺癌1例,胰腺癌1例,子宫内膜癌1例,横纹肌肉瘤1例。rAdp53给药方案为1×1012VP/次,每周1次,4次为1疗程。给药途径包括瘤内注射、支气管内喷洒、腹腔内注射、动脉灌注和静脉滴注。联合化疗18例,联合放疗2例,联合同期放、化疗1例,联合腹部热疗和吉非替尼1例,联合免疫治疗1例,rAdp53单药治疗1例。结果:24例患者中因早期进展而停药1例,接受1疗程治疗20例,2疗程治疗2例,5疗程治疗1例。在可评价的21例中,部分缓解(PR)5例,稳定(SD)5例,进展(PD)11例,有效率23.8%(5/21),疾病控制率47.6%(10/21)。常见不良反应为自限性、I～II度注射部位疼痛、寒颤、发热和肌肉酸痛。III度发热2例,联合化疗者发生III～IV度骨髓抑制4例,骨痛加剧2例,一过性低血压1例。结论:晚期实体瘤患者可耐受rAdp53治疗,有必要进一步设计临床试验,确定rAdp53联合常规治疗的有效性。

AIM： Recombinant human adenovirus-p53 injection （rAd-p53） is the first marketed gene therapeutic drug worldwide. This study aimed to evaluate the safety and primary efficacy of rAd-p53 administrated on advanced solid tumors. METHODS： 24 patients with advanced solid tumor treated with rAd-p53 were reviewed, including 5 cases of renal carcinoma, 4 of nasopharyngeal carcinoma, 4 of colorectal carcinoma, 2 of melanoma, 1 of non-small-celllung cancer, 1 of esophageal carcinoma, 1 of gastric cardia carcinoma, 1 of thymic carcinoma, 1 of duodenal carcinoma, 1 of thyroid carcinoma, 1 of pancreatic carcinoma, 1 of endometrial carcinoma and 1 of rhabdomyosarcoma. RAd-p53 was weekly administrated at the dose of 1×10^12 VP, and 4 times of administration was defined as one cycle. Administration approach included intratumoral injection, intrabronchial drop in, intraperitoneal injection, intra-arterial infusion and intravenous drip. Combined therapy was given with chemotherapy in 18 cases, radiotherapy in 2, concomitant chemotherapy and radiotherapy in 1, abdominal thermotherapy and orally gefitinib in 1, cytokine immunotherapy in 1 and without combination therapy in 1. RESULTS： 23 cases underwent 35 cycles of therapy except for 1 case discontinued because of early progression. Among the 21 evaluable cases 5 PR, 5 SD and 11 PD were observed. Overall response rate was 23.8% （5/21） and disease control rate was 47.6% （10/21）. Grade Ⅰ-Ⅱ injection site pain, chill, fever and myalgia were the most frequent side effects. Grade Ⅲ fever developed in 2 cases and grade Ⅲ-Ⅳ myelosuppression in 4 cases combined with chemotherapy. Fuahennore, severe ostealgia occurred in 2 cases and transient hypotension in 1. CONCLUSION： RAd-p53 is tolerable in patients with advanced solid tumor. A further randomized clinical trial is necessary to confirm the antitumor activity of rAd-p53 combined with conventional strategies.