Beyond intravenous delivery: choosing better administration routes for oncologic drugs

Intravenous delivery remains the dominant paradigm in oncology, but even with precision medicine few drugs pass late stage clinical trials. Karthik Chellappan proposes that early exploration of better administration routes could make all the difference.

Over the last decade, the shift towards “precision” medicine has led to increasing use of biomarkers and, more recently, next-generation sequencing to guide therapy selection. Here we argue that there is another, underexplored dimension to “precision” oncology: the adoption of targeted alternatives to intravenous infusion, such as intratumoral delivery, delivery via locoregional vasculature and lymphatic delivery.

The approach we propose broadens opportunities in drug design and can enhance the effects of existing targeting approaches employed in the pharmaceutical industry. First, by avoiding systemic toxicity, targeted administration via alternative routes may enlarge the design space for oncologic drugs, thus leading to drug candidates with improved efficacy. Second, targeted administration also has the potential to enhance the effects of other, formulation-based targeting technologies by helping drug entities overcome the physiological barriers that hinder drug transport and retention.

However, as we explain below, early preclinical assessment of different targeted routes is essential to increase the likelihood of successful therapeutic outcomes. Moreover, the effectiveness of a targeted administration route is heavily influenced by the device-specific delivery parameters, such as fluid pressures and flow rates, and therefore requires multidisciplinary understanding of tissue biomechanics and anatomic and fluidic principles to complement medical device design and development.

Constraints imposed by intravenous delivery

Currently, the most widely accepted route of delivery for oncologic drugs is intravenous administration. Most monoclonal antibodies and chemotherapies, regardless of their indications, are delivered through this…