Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction
Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction
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DOI：
10.1073/pnas.1210662109
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发表时间：
2012-11-20
影响因子：
11.1
通讯作者：
Illei, Gabor G.
中科院分区：
文献类型：
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作者：
Baum, Bruce J.;Alevizos, Ilias;Illei, Gabor G.
对于放射治疗肿瘤学组晚期2-3级毒性的幸存头颈癌患者，没有常规治疗方法治疗唾液腺功能减退。我们进行了一项I期临床试验，采用开放标签、单剂量、剂量递增设计（AdhAQP 1载体; 4个剂量层，每个腺体4.8 × 10（7）至5.8 × 10（9）载体颗粒），在11名受试者中测试血清型5腺病毒介导的水通道蛋白-1 cDNA转移至单个先前辐照过的腮腺的安全性和生物学功效。按计划时间间隔对治疗受试者进行随访。测量多个安全性参数，并通过测量腮腺唾液流速评价生物学疗效。使用视觉模拟量表评估症状。在报告的42天研究期间，所有受试者均耐受载体递送和研究程序。未发生死亡、严重不良事件或剂量限制性毒性。一般来说，发生的不良事件很少，所有事件都被认为是轻度或中度的。在测量的任何临床化学和血液学参数中均未发现一致的变化。在6名受试者中观察到客观缓解，所有受试者均接受了
No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 x 10(7) to 5.8 x 10(9) vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses