基因工程腺病毒(H101)瘤内注射联合化疗治疗头颈部及食管鳞癌的Ⅲ期临床研究

Phase ⅢRandomized Clinical Trial of Intratumoral Injection of E1B Gene-deleted Adenovirus (H101) Combined with Cisplatin-based Chemotherapy in Treating Squamous Cell Cancer of Head and Neck or Esophagus

背景与目的:H101是利用基因重组技术得到的一种删除了E1B部分基因片段的溶瘤腺病毒,其在一定剂量范围内对肿瘤有明显的抑制作用。本研究目的是比较H101瘤内注射联合顺铂(cisplatin,DDP)+5-氟尿嘧啶(5-fluorouracil,5-FU)或阿霉素(adriamycin,ADM)+5-FU方案化疗与单纯化疗对头颈、食管鳞癌的治疗效果及毒副作用。方法:160例入选患者,根据过去化疗史分别选定不同化疗方案。未用过PF方案化疗或用过PF方案有效者采用PF方案化疗,已用过PF方案无效者则采用AF方案化疗。采用多中心随机对照分组,分别加用(A组)或不加用(B组)肿瘤浅表病灶内注射H101。两组均为21天一个周期,所有患者至少接受2个周期的治疗。结果:完全符合方案标准的病例123例,A1组(PF+H101)有效率为78.8%,B1组(PFonly)为39.6%,A2组(AF+H101)为50%(7/14),B2组(AFonly)50%(2/4)。A1、B1组间以及A1+A2、B1+B2组间疗效差异有显著性(P=0.000)。45.7%病例出现轻～中度发热,28.3%出现注射局部反应,9.8%出现流感样症状。结论:H101注射液瘤内局部注射联合化疗的客观有效率比单纯化疗组高,显示H101瘤内注射对于头颈、食管鳞癌具有明确的治疗作用,且具有较高的安全性。

BACKGROUND &OBJECTIVE: H101 is an E1B-55 kDa gene-deleted repl ic ation-selective adenovirus,which showed a significant antitumor activity. This study was to compare effects and toxicities of intratumoral H101 injection combi ned with cisplatin plus 5-fluorouracil (PF) regimen or adriamycin plus 5-fluor ouracil (AF) regimen versus PF or AF regimen alone in treating patients with hea d and neck or esophagus squamous cell cancer. METHORDS: A total of 160 patients were recruited. PF regimen (cisplatin 20 mg/m2 ivgtt,qd×5d; 5-fluorouracil 500 mg/m2 ivgtt,qd×5d) was administered to patients have no history of PF chemothe rapy,or sensitive to PF chemotherapy,while AF regimen (adriamycin 50 mg/m2 iv,d1 ; 5-fluorouracil 500 mg/m2 ivgtt,qd×5d) was administered to patients didnt r esponse to PF regimen. All patients were randomized to either receive intratumor al H101 injection (5.0×1011-1.5×1012 VP/day for 5 consecutive days every 3 we eks) or not. Treatment repeated every 3 weeks,all patients have to receive at le ast 2 cycles of chemotherapy. RESULTS: Among 123 accordant patients,overall resp onse rate of PF plus H101 group (group A1) was 78.8%(41/52),of PF alone group ( group B1) was 39.6%(21/53),of AF plus H101 group (group A2) was 50.0%(7/14),of AF alone group (group B2) was 50.0%(2/4). Differences of response rates betwee n group A1 and group B1,between group A1+A2 and group B1+B2 were significant ( P=0.000). Main side effects were fever (45.7%),injection site reaction (28.3%) ,and influenza-like symptoms (9.8%). CONCLUSION: Intratumoral H101 injection s howed a distinct efficacy in patients with squamous cell cancer of head and neck or esophagus,and was relatively safe.