瘤内注射重组溶瘤病毒联合吉西他滨化疗治疗中晚期胰腺癌l9例疗效观察

Intra-tumoral injection of E1B gene-deleted adenovirus combined with gemcitabine for unresectable pancreatic carcinoma： 19 cases analysis

目的探讨内镜超声引导下瘤体内注射重组溶瘤病毒（H101）联合吉西他滨化疗治疗中晚期胰腺癌的疗效及安全性。方法选择无手术指证的未行抗肿瘤治疗的中晚期胰腺癌患者共19例，于内镜超声引导下行H10I瘤体内注射，并于注射后第3、10、17d行吉西他滨静脉化疗（1000mg∥m^2），共2个疗程。记录注射前后肿瘤体积，评定疗效；记录患者疼痛及Kamofsky评分变化、不良反应及并发症发生率、生存期。结果12例肿瘤体积缩小5．3％～69．7％，但治疗前后的平均体积差异无统计学意义（P=0．275）。19例患者均完成2周期联合治疗。3例（15．8％）部分缓解；10例（52．6％）稳定；无治愈患者。治疗后平均疼痛评分明显低于治疗前（3．1±1．7比3．9±1．6，P=0．004）。治疗后Karnofsky评分明显提高[（68．4±12．1）％比（61．1±9．9）％，P=0．003）]。未发生与操作相关的并发症，与治疗相关的不良反应主要为发热与腹泻。19例患者生存期为2．5～10个月，随访截止时9例患者仍存活。结论内镜超声引导下瘤体内注射重组溶瘤病毒联合吉西他滨化疗治疗中晚期胰腺癌的方法是安全、有效的，能改善患者生存质量、降低疼痛评分。

Objective To evaluate the efficacy and tolerability of EUS-guided intra-tumoral injection of E1 B gene-deleted adenovirus （H101） combined with intravenous gemeitabine for unresectable pancreatic carcinomas. Methods Nineteen patients with advanced adenocarcinoma of the pancreas who were not resectable and never to anti-cancer treatment were enrolled in this study. Each patient underwent two sessions of EUS-gnided H101 intra-tumoral injection in combination with gemcitabine （ i. v. , 1000 mg/m^2 , d3, 10, 17）. The tumor size before and after H101 intra-tumoral injection were recorded for efficacy assessment. The changes of pain score and KPS, adverse effects and complication rates, survival were estimated. Results The tumor size decreased in twelve patients by 5.3% - 69.7% , but the difference was not statistically significant （P =0.275）. All of nineteen patients completed two cycles of combination trea＇;ment. Among them, 3 （ 15.8% ） achieved partial response, 10 （52.6%） had stable disease, and none had complete response. The mean pain score after injection was significantly lower than that before injection （3.1 ±1.7 vs. 3.9±1.6, P = 0.004）. KPS after injection was significantly increased more than that before injection [ （68.4 ±12.1 ）% vs. （61.1± 9.9）%, P =0. 003）]. There was no complication associated with the procedure. Major adverse effects associated with H101 injection were fever and diarrhea. The survival time was 2.5 to 10 months. Nine patients were still alive. Conclusions EUS-guided E1B gene-deleted adenovirus intra-tumral injection in unresectable pancreatic carcinomas is feasible and well tolerated in combination with intravenous gemcitabine, which can improve the quality of life and decrease the pain score.