Optimizing pharmacokinetics of intravesical chemotherapy for bladder cancer

Abstract

Non-muscle-invasive bladder cancer (NMIBC) remains one of the most common malignancies and is associated with considerable treatment costs. Patients with intermediate-risk or high-risk disease can be treated with intravesical BCG, but many of these patients will experience tumour recurrence, despite adequate treatment. Standard of care in these patients is radical cystectomy with urinary diversion, but this approach is associated with considerable morbidity and lifestyle modification. As an alternative, perioperative intravesical chemotherapy is recommended for low-risk papillary NMIBC, and induction intravesical chemotherapy is an option for patients with intermediate-risk NMIBC and BCG-unresponsive NMIBC. However, poor pharmaceutical absorption and drug washout during normal voiding can limit sustained drug concentrations in the urothelium, which reduces efficacy, and small-molecule chemotherapeutic agents can be absorbed through the urothelium into the bloodstream, leading to systemic adverse effects. Several novel drug delivery methods - including hyperthermia, mechanical sustained released devices and nanoparticle drug conjugation - have been developed to overcome these limitations. These novel methods have the potential to be combined with established chemotherapeutic agents to change the paradigm of NMIBC treatment.