p53基因联合热放疗治疗晚期软组织肉瘤的临床研究

Clinical Effect of Recombinant Adenovirus-p53 Combined with Hyperthermia for Advanced Soft Tissue Sarcoma

为评价重组人p53腺病毒注射液(rAdp53)结合热疗治疗软组织肉瘤的疗效及安全性,2001年10月至2012年6月,采用rAdp53,结合热疗放疗,治疗晚期软组织肉瘤30例。基因治疗采用瘤内注射或腹腔灌注rAdp53,每周1次,每次1×1012VP,平均8次。所有患者均配合热疗,平均热疗8次。放疗每次2Gy,每周5次,剂量为16～70Gy/8～35次/2～8周,平均56.3Gy。30例患者在治疗前后观测肿瘤变化,以CT评价治疗后2个月的疗效。结果表明,病灶缩小超过或等于50%者9例,介于25%～50%者8例,缩小小于25%者12例;病灶增大者1例。生存率1年为(58.6±0.091)%,2年为(22.4±0.079)%,3年为(11.2±0.069)%,4年为(5.6±0.052)%。30例患者共接受216次rAdp53瘤内注射,除1例出现过性发热外,未发现其他不良反应,未影响热疗和放疗。研究表明,软组织肉瘤瘤内注射rAdp53结合热疗、放疗安全、有效。rAdp53是一种很有潜力的治疗恶性软组织肿瘤的基因治疗药物。

In order to evaluate the efficacy and safety of recombinant adenovirus-p53 （rAdp53） combined with hyperthermia for advanced soft tissue sarcoma, from Nov. 2001 to Jun. 2012, 30 patients with advanced soft tissue sarcoma enrolled in the clinical study on Gendicine combined with hyperthermia or hyperthermia plus radiotherapy. Gendicine, recombinant adenovirus-p53, is an E1 substituted replication-incompetent recombinant adenovirus encoding the human wild-type p53 gene. Thirty patients were intratumorally injected or intra-abdominal cavity perfused with Gendicine solution of lxl01Wp （Virus Particle） once a week with a total eight times on average. Two days after injection, all patients were combined with. hyperthermia usually once or twice a week for total eight times on average. Among them, 12 patients were concurrently added with irradiation with the conventional fractionation of 2Gy/f, five fractions a week to a total dose of 16 Gy-70 Gy/8 times-35 times/2 weeks-8 weeks, 56.3Gy on average. Patients were monitored for adverse event and tumors were monitored for response. Two months after treatment, the effective rate was performed by the immediate response rate on CT at the validation point. Among the 30 patients, tumor mass shrinks more than 50% in the nine cases,25%-50% in eight cases,less than 25% in 12 cases, nidus growth in one case. One year survival rate is （58.6±0.091）% ,2 year survival rate is （22.4±0.079）% ,3 year survival rate is （11.2±0.069）%, and 4 year survival rate is （5.6±0.052）%. Thirty patients with advanced soft tissue sarcoma have received hyperthermia and multiple intratumorally injection of Gendicine, dose-limiting toxicity and adverse events are not noted, except transient fever after Gendicine administration in one case. The treatment with intratumoral injecting of Gendicine combined hyperthermia for advanced soft tissue sarcoma is safe and effective. The results support that rAdp53 is a potentially effective gene therapeutic agent for the soft tissue sarcoma treatment.