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

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。rAd-p53 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,rAd-p53 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rAd-p53 治疗, 有必要进一步设计临床试验, 确定rAd-p53 联合常规治疗的有效性。

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

AIM: Recombinant human adenovirusp53 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 ×1012 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, abdomi-nal 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 myalgiawere the most frequent side effects.Grade III fever developed in 2 cases and grade III-IV myelosuppression in 4 cases combined with chemotherapy.Furthermore, 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.