Department of Pharmaceutics, School of Pharmacy, University College London, UK.
Department of Pharmaceutics, School of Pharmacy, University College London, UK; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt.
Eur J Pharmacol. 2022 Jul 5;926:175024. doi: 10.1016/j.ejphar.2022.175024. Epub 2022 May 14.
Bladder cancer is the 10th most frequently diagnosed cancer worldwide with 5-year survival rate around 70%. The current first-line treatment for non-muscle invasive bladder cancer is transurethral resection of bladder tumours followed by intravesical Mycobacterium Bovis Bacillus Calmette-Guérin (BCG) immunotherapy. However, tumor recurrence rate is still high ranging from 31% to 78% within five years. To avoid radical cystectomy, intravesical combination therapies have been developed as salvage treatments to overcome BCG failure. Recent advances in diagnostics thanks to tumor molecular profiling and in treatment such as development of immunotherapies provides more treatment options beyond BCG treatment. This also goes hand-in hand with formulation advances to deliver these new therapies where traditional drug delivery systems might not be suitable, which in turn is completed by challenges to deliver drugs via the intravesical route. In this article the aim was to provide an in-depth analysis of the current developments of intravesical combination therapies, ranging from relatively simple combinations of mixing existed intravesical therapeutic agents (immunotherapies and chemotherapies) to the combined formulations containing advanced gene therapies and targeted therapies, with special focus on therapies that have made it to the clinical trial stage. In addition, recent attempts to utilize device-assisted treatments and novel drug delivery platforms are included. This review also highlights the limitations that still need to be overcome such as the inadequate studies on newly explored drug carriers and proposes potential directions for future work to overcome BCG-failure.
膀胱癌是全球第 10 大常见癌症，5 年生存率约为 70%。目前，非肌肉浸润性膀胱癌的一线治疗方法是经尿道膀胱肿瘤切除术，随后进行卡介苗（BCG）膀胱内免疫治疗。然而，肿瘤复发率仍然很高，五年内复发率为 31%至 78%。为避免根治性膀胱切除术，已经开发了膀胱内联合疗法作为挽救治疗方法，以克服 BCG 治疗失败。由于肿瘤分子谱分析和免疫疗法等治疗方法的进展，目前有了更多的治疗选择，而不仅仅是 BCG 治疗。这也与制剂的进步齐头并进，以提供这些新疗法，而传统的药物输送系统可能不适合，这反过来又需要通过膀胱内途径输送药物的挑战。本文旨在深入分析当前膀胱内联合疗法的发展，范围从相对简单的混合现有膀胱内治疗药物（免疫疗法和化学疗法）到包含先进基因疗法和靶向疗法的联合制剂，特别关注已进入临床试验阶段的疗法。此外，还包括最近利用设备辅助治疗和新型药物输送平台的尝试。本综述还强调了仍然需要克服的局限性，例如对新探索的药物载体的研究不足，并提出了克服 BCG 失败的潜在未来工作方向。
