ASCO2013: 第三军医大学杨茂林等证实rAd-p53在口腔颌面部肿瘤中的应用价值

背景:曾于1998年左右针对基因治疗产品(Gendicine, rAd-p53)进行的市场预研结果表明，该产品在多模式治疗方案治疗鳞状细胞鼻咽癌中具有疗效。迄今Gendicine已在超过40种肿瘤类型的治疗中得到成功应用。随着多年来在优化联合治疗手段方面取得的进展，有必要进行一项中期疗效研究。本报告对临床IV期研究进行了归纳。
方法：根据GCP标准对患者进行了筛选、干预及分配，并得到了统计学分析支持。本项开放性结局、随机、对照研究招募对象来自中国多家医院(n=30)，为晚期(III/IV期)口腔颌面部肿瘤(OFC)患者(2009.7--2012.06)。两治疗组分别为rAd-p53+化疗组(GT+CT) (n=743)，以及单纯CT组(n=232)。患者剔除率分别为20.81% (n=128) 及13.9% (n=28)。瘤内病毒颗粒给药剂量为109 (肿瘤细胞/cm2瘤体面积) x 面积x100 (病毒感染复数, MOI)，在第1-28d中，每3d给药一次，共给药10次。在联合GT同步治疗时，在第7-11d联合5-氟尿嘧啶(5-FU, 250 mg/m2/d)治疗, 在第25-29d联合卡铂治疗(KP,400 mg/m2/d, i.v.)，在第 7、14、25、32d联合甲氨蝶呤治疗(MTX, 50mg/m2 /d)。对照组患者则接受5-FU、KP及MTX治疗。
结果：接受GT+CT方案对晚期OFC患者的疗效及QoL均得到了显著改善，该结果与之前的II/ III期研究结论一致。
结论：本研究证明了rAd-p53用于辅助治疗时的安全性及有效性。副作用类型主要为自限性低度至轻度发热。GT-CT联合治疗方案的完全缓解率(CR)提高了21.38%，减轻率(RR)提高了11.53%，临床获益率提高了20.82%。本研究将继续进行长期随访。
Multicenter, open-end, randomized controlled study using P53 gene recombinant adenovirus injection (rAd-p53) combined with chemotherapy for orofacial carcinoma (OFC): Phase IV clinical trial—Progress report and conclusion.
Abstract
Background: The gene therapy product (Gendicine, rAd-p53) had pre-market studies done around 1998 indicated its efficacy in the treatment of squamous cell nasopharyngeal carcinoma in multi-modality treatment regimen. Gendicine has been used successfully in treating over 40 cancer types since then. With the advancement in optimization of combined treatment methods over the years, there was a need for a medium term efficacy study. This report summarizes our phase IV study. Methods: Patient selection, intervention and allocation were done according to GCP and supported by statistical analysis. Orofacial cancer (OFC) patients of advanced stages (III/IV) from multiple hospitals (n=30) in China were recruited for this open-end, randomized, controlled study (2009.7--2012.06). The 2 groups were rAd-p53+chemotherapy (GT+CT) (n=743) and CT alone (n=232). Patient exclusion rate were 20.81% (n=128) and 13.9% (n=28) respectively. Virus particles were delivered intra-tumorally at a dose of 109 (tumor cell/cm2 tumor area) x area x100 (virus multiplicity of infection, MOI), every 3d totally 10 times on d 1-28 inclusive. In synchrony with GT, 5-fluorouracil (5-FU, 250 mg/m2/d), on d 7-11 and d 25-29 along with carbocisplatin (KP, 400 mg/m2/d, i.v.), and with methotrexate (MTX, 50mg/m2 /d) on d 7, 14, 25, 32 were administered. The control group received 5-FU, KP and MTX. Results: For advanced OFC treated with GT+CT, the efficacy and QoL were significantly (p<=0.001) improved, the result was in accordance with our phase II/ III studies. Conclusions: This study proved rAd-p53 when used as an adjunct is safe and efficacious. The side-effect was mostly self-limiting low-grade to mild fever. The combined treatment modality had complete remission (CR) improved by 21.38%, relief ratio (RR) by 11.53% and clinical benefit ratio by 20.82% over GT-CT. Long-term follow-up will be continued.