An attenuated adenovirus, ONYX-015, as mouthwash therapy for premalignant oral dysplasia
An attenuated adenovirus, ONYX-015, as mouthwash therapy for premalignant oral dysplasia
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DOI：
10.1200/jco.2003.03.544
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发表时间：
2003-12-15
影响因子：
45.3
通讯作者：
Vokes, EE
中科院分区：
文献类型：
--
作者：
Rudin, CM;Cohen, EEW;Vokes, EE
目的：口腔上皮的发育不良病变是口腔癌的先兆。相当比例的口腔发育异常病变在p53反应通路中存在功能缺陷。ONYX-015腺病毒对携带p53依赖性信号传导途径缺陷的细胞具有选择性细胞毒性。目前的研究试图建立ONYX-015的可行性和活性局部给药作为漱口水的患者临床上明显的和组织学异常病变的口腔mucosa.Patients和方法：共22例患者（19个评估患者）被纳入研究。ONYX-015以三种不同的时间表给予连续队列。对受累粘膜进行活检，以评估组织学反应和恶性潜能的推定标志物（包括p53、细胞周期蛋白D1和Ki-67）表达的变化。血清学进行测量antiadenoviraltiters.Results：组织学决议的发育不良被认为是在7（37%）的19例，和一个额外的患者的发育不良的等级得到改善。大多数反应是短暂的。未观察到大于2级的毒性（1例患者发生发热事件）。只有1/7的患者在治疗期间循环抗腺病毒抗体滴度增加。虽然缓解和耐药病灶在基线时的平均p53染色相似，但组织学缓解与p53阳性随时间推移而降低相关。未观察到细胞周期蛋白D1或Ki-67的显著变化。病毒复制被证实在两个三个病变examined.Conclusion：这种新的方法来预防癌症是可以忍受的，可行的，并具有明显的活性。(C)2003年，美国临床肿瘤学会。
Purpose: Dysplastic lesions of the oral epithelium are known precursors of oral cancer. A significant proportion of oral dysplastic lesions have functional defects in p53 response pathways. The ONYX-015 adenovirus is selectively cytotoxic to cells carrying defects in p53-dependent signaling pathways. The current study sought to establish the feasibility and activity of ONYX-015 administered topically as a mouthwash to patients with clinically apparent and histologically dysplastic lesions of the oral mucosa.Patients and Methods: A total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX-015 was administered on three different schedules to consecutive cohorts. Biopsies of the involved mucosa were performed to evaluate histologic response and changes in expression of putative markers of malignant potential, including p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral titers.Results: Histologic resolution of dysplasia was seen in seven (37%) of 19 patients, and the grade of dysplasia improved in one additional patient. The majority of responses were transient. No toxicity greater than grade 2 (febrile episode in one patient) was observed. Only one of seven patients demonstrated an increase in circulating antiadenoviral antibody titer while on therapy. Although responding and resistant lesions had similar mean p53 staining at baseline, histologic response correlated with a decrease in p53 positivity over time. Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication was confirmed in two of three lesions examined.Conclusion: This novel approach to cancer prevention is tolerable, feasible, and has demonstrable activity. (C) 2003 by American Society of Clinical Oncology.