Loco-regional drug delivery in oncology: current clinical applications and future translational opportunities

Abstract

IntroductionDrug-based treatment regimens for cancer are often associated with off-target toxic side effects and low penetration of the drug at the tumor site leading to patient morbidity and limited efficacy. Locoregional drug delivery has the potential to increase efficacy while concomitantly reducing toxicity. Areas coveredClinical applications using loco-regional delivery include intra-arterial drug delivery in retinoblastoma, direct intra-tumoral (IT) injection of ethanol for ablation in hepatocellular carcinoma (HCC) and the use of HIPEC in peritoneal carcinomas. In recent years, there has been a significant increase in both approved products and clinical trials, with a particular emphasis on drug delivery platforms such as drug eluting beads for HCC and hydrogel platforms for intravesical delivery in bladder cancer. Expert opinionDevelopment of loco-regional drug delivery systems has been slow, limited by weak clinical data for early applications and challenges relating to dosing, delivery and retention of drugs at the site of action. However, there is increasing focus on the potential of loco-regional drug delivery when combined with bespoke drug delivery platforms. With the growth in immunotherapies, the use of IT delivery to drive priming of the anti-tumor response has opened up a new field of opportunity for locoregional drug delivery.

Phase 1/2 Trial Results of a Large Surface Area Microparticle Docetaxel for the Treatment of High-Risk Nonmuscle-Invasive Bladder Cancer

“…Local treatment of solid tumors has the potential to overcome the limitations of intravenous chemotherapy 9,10 by increasing tumor dwell time and reducing systemic toxicities. Sharma et al reported that locally advanced pancreatic cancer patients demonstrated regression or lack of disease progression following intratumoral treatment with similar large surface area microparticle paclitaxel (LSAM-PTX), 11 and Verco et al reported that local administration of LSAM-PTX exposed primary tumors to therapeutic levels of chemotherapeutic for several weeks.…”

Local administration of large surface area microparticle docetaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects: preclinical and clinical studies

“…The maximum tolerated doses of IV chemotherapies are often limited by toxicities such as cytopenia due to bonemarrow suppression [17]. In contrast, local administration of chemotherapy allows for a substantial reduction in systemic exposure and drug-related systemic adverse events [2,12,18]. Clinical results of systemic combinations of chemotherapy and immunotherapy have often been disappointing [19].…”

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

“…As a product with both clinical transformation significance and commercial transformation value, 3D macroscale scaffolds also need to think about mass production and patient compliance [ 37 , 227 ]. Going forward, the 3D macroscale biomaterial-based immunotherapies with great translational potential will open more avenues of modulating the immune responses against more sophisticated diseases.…”