A Phase 1b Clinical Study of Intravesical Photodynamic Therapy in Patients with Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer.
A Phase 1b Clinical Study of Intravesical Photodynamic Therapy in Patients with Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer.
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一项关于膀胱内光动力疗法用于卡介苗无反应的非肌层浸润性膀胱癌患者的1b期临床研究 。
DOI：
10.1016/j.euros.2022.04.015
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发表时间：
2022-07
影响因子：
2.5
通讯作者：
Jewett, Michael A. S.
中科院分区：
文献类型：
--
作者：
Kulkarni, Girish S.;Lilge, Lothar;Nesbitt, Michael;Dumoulin-White, Roger J.;Mandel, Arkady;Jewett, Michael A. S.
关键词：
使用TLD - 1433进行光动力疗法治疗卡介苗（BCG）无反应的膀胱癌，似乎安全性良好，药代动力学特征也可接受。在1b期试验中也观察到了有效性信号，因此有必要开展2期试验。
一项关于光敏剂TLD - 1433介导的光动力疗法（PDT）的1b期研究，在卡介苗（BCG）无反应的非肌层浸润性膀胱癌（NMIBC）患者中展开。
该研究的主要目标是评估光动力疗法的安全性和耐受性，次要目标包括：（1）TLD - 1433的药代动力学（PK）特性；（2）疗效，通过在最大推荐起始剂量（0.35毫克/平方厘米膀胱表面积）和治疗剂量（0.70毫克/平方厘米）下接受治疗的患者在90天和180天的无复发生存率和完全缓解（CR）情况进行评估。
6名卡介苗无反应的患者参与了一项开放性、单臂、剂量递增的光动力疗法研究。术前将TLD - 1433膀胱内灌注60分钟。光动力疗法在全身麻醉下进行，通过膀胱内照射膀胱壁，采用绿光（520纳米），剂量为90焦耳/平方厘米。
通过标准膀胱镜检查和细胞学检查对患者进行长达18个月的随访，以评估复发时间。
所有患者对光动力疗法耐受性良好。所有患者至少经历过一次≤2级不良事件（AE）。没有患者死亡或出现光敏反应。最常见的不良事件是中度膀胱刺激症状，在治疗后的最初几周内缓解。不良事件与TLD - 1433的剂量无关。TLD - 1433分别在24小时和72小时内从尿液和血浆中清除。在接受治疗剂量的3名患者中，有2名在180天时达到完全缓解，且在18个月时仍维持缓解状态。另一名患者在138天时被诊断为转移性疾病。
使用TLD - 1433进行光动力疗法治疗卡介苗无反应的非肌层浸润性膀胱癌似乎是安全的。全剂量光敏剂带来的早期疗效信号令人鼓舞，有必要开展2期试验进行研究。所获得的安全性和药代动力学结果支持根据需要连续进行光动力疗法治疗的可能性。
使用TLD - 1433进行光动力疗法治疗卡介苗（BCG）无反应的膀胱癌似乎安全有效。
Photodynamic therapy for bacillus Calmette-Guérin–unresponsive bladder cancer with TLD-1433 appears safe with an acceptable pharmacokinetic profile. A signal for effectiveness was also seen in the phase 1b trial, thus warranting pursuit of a phase 2 trial. A phase 1b study of photosensitizer TLD-1433–mediated photodynamic therapy (PDT) was performed in bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients. The primary objectives were safety and tolerability of PDT, with secondary objectives of (1) pharmacokinetic (PK) properties of TLD-1433 and (2) efficacy, as evaluated by recurrence-free survival and complete response (CR) at 90 and 180 d for patients treated at the maximum recommended starting dose (0.35 mg/cm2 bladder surface area) and the therapeutic dose (0.70 mg/cm2). Six BCG-unresponsive patients were enrolled in an open-label, single-arm, dose-escalating study of PDT. TLD-1433 was instilled intravesically for 60 min preoperatively. PDT was performed under general anesthesia using intravesically delivered irradiation of the bladder wall with green light (520 nm) to a dose of 90 J/cm2. Patients were followed by standard cystoscopy and cytology for up to 18 mo to assess time to recurrence. PDT was well tolerated by all patients. All patients experienced at least one grade ≤2 adverse event (AE). There were no patient deaths or light sensitivity reactions. The most common AE was moderate bladder irritability, which resolved within the first weeks after treatment. AEs were independent of the TLD-1433 dose. TLD-1433 was cleared in the urine and from the plasma within 24 and 72 h, respectively. Of three patients treated at the therapeutic dose, two achieved a CR at 180 d, which was durable at 18 mo. The other patient was diagnosed with metastatic disease at 138 d. PDT with TLD-1433 appears safe for the treatment of BCG-unresponsive NMIBC. Early efficacy signals from full-dose photosensitizer are encouraging and warrant phase 2 trial investigation. The safety and PK results obtained support the potential for administration of consecutive PDT treatments as required. Photodynamic therapy with TLD-1433 appears to be safe and effective for the treatment of bacillus Calmette-Guérin (BCG)-unresponsive bladder cancer.
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DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
6.6
作者：
Steinberg, Ryan L.;Thomas, Lewis J.;O'Donnell, Michael A.
通讯作者：
O'Donnell, Michael A.
影响因子：
2.1
作者：
DHALLEWIN, MA;BAERT, L
通讯作者：
BAERT, L
DOI：
10.1007/s10928-014-9392-y
发表时间：
2014-12-01
影响因子：
2.5
作者：
Jawien, Wojciech
通讯作者：
Jawien, Wojciech
DOI：
10.1016/s1470-2045(20)30540-4
发表时间：
2021-01
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Boorjian SA;Alemozaffar M;Konety BR;Shore ND;Gomella LG;Kamat AM;Bivalacqua TJ;Montgomery JS;Lerner SP;Busby JE;Poch M;Crispen PL;Steinberg GD;Schuckman AK;Downs TM;Svatek RS;Mashni J Jr;Lane BR;Guzzo TJ;Bratslavsky G;Karsh LI;Woods ME;Brown G;Canter D;Luchey A;Lotan Y;Krupski T;Inman BA;Williams MB;Cookson MS;Keegan KA;Andriole GL Jr;Sankin AI;Boyd A;O'Donnell MA;Sawutz D;Philipson R;Coll R;Narayan VM;Treasure FP;Yla-Herttuala S;Parker NR;Dinney CPN
通讯作者：
Dinney CPN