膀胱内的nadofaragene firadenovec基因治疗BCG-unresponsive non-muscle-invasive膀胱癌:单臂,非盲、repeat-dose临床试验。
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Boorjian SA Alemozaffar M, Konety BR,海岸ND Gomella LG,令Kamat, Bivalacqua TJ,蒙哥马利JS Lerner SP,巴斯比我,Poch M,变脆PL,斯坦伯格GD, Schuckman AK, TM, Svatek RS, Mashni J Jr, Lane BR Guzzo TJ, Bratslavsky G,卡什,树林,布朗克,慢跑D, Luchey,罗坍Y, Krupski T,曼巴,威廉姆斯MB, Cookson女士,基冈KA, Andriole GL Jr Sankin AI,博伊德,奥唐纳,Sawutz D, Philipson R,科尔R, Narayan VM,珍惜FP, Yla-Herttuala年代,帕克NR, Dinney尼泊尔共产党
膀胱内的nadofaragene firadenovec基因治疗BCG-unresponsive non-muscle-invasive膀胱癌:单臂,非盲、repeat-dose临床试验。
柳叶刀杂志。2021年1月,22 (1):107 - 117。doi: 10.1016 / s1470 - 2045 (20) 30540 - 4。Epub 2020年11月27日。
- PubMed ID
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33253641 (在PubMed]
- 文摘
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背景:卡介苗是最有效的治疗高危non-muscle-invasive膀胱癌。Nadofaragene firadenovec(也称为rAd-IFNa / Syn3)是一个replication-deficient重组腺病毒,提供人体干扰素alfa-2b cDNA膀胱上皮,小说和膀胱内的治疗BCG-unresponsive non-muscle-invasive膀胱癌。我们旨在评估其疗效患者BCG-unresponsive non-muscle-invasive膀胱癌。方法:在这个阶段3、多中心、非盲、repeat-dose在33个研究中心(医院和诊所)在美国,我们招募患者18岁或以上,BCG-unresponsive non-muscle-invasive膀胱癌和东部合作肿瘤组状态2或更少。患者被排除在外,如果他们有上尿路疾病,前列腺尿道移行细胞癌,lymphovascular入侵,micropapillary疾病,或肾盂积水。符合条件的患者接受一个膀胱内的75毫升剂量的nadofaragene firadenovec (3 x 10(11)病毒颗粒/毫升)。重复给药在3个月、6和9是在缺乏高档复发。主要终点是完整的反应原位癌患者在任何时间T1(有或没有高档的助教或肿瘤)。指定的零假设的完全缓解率不到27%在这个队列。功效分析是在按方案完成人口,只包括病人严格会议BCG-unresponsive定义。 Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53.4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45.5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.
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