Improving the Dosing Schedules of Targeted Anticancer Agents.

Abstract

Beyond developing new agents, cancer treatment can also be optimized by modifying the dosing regimen of approved drugs. Academic teams have experimented with different ways of improving drug regimens, leading to off-label practices for therapeutic and/or economic purposes, and currently, drug regulatory agencies have begun to reappraise this often-neglected topic. This concept also considers the patient's perspective in terms of quality of life and convenience, including the concept of time toxicity. Overall, the optimization of drug dosing of anticancer agents may be viewed on three sides: the improvement of the benefits/risks balance (patient), the improvement of the convenience of the treatment (patient, healthcare professionals), and the mitigation of the financial impact (health insurance, patient). Examples of dose reassessments of targeted therapies (approved since 1997) are chosen to illustrate the context. Suboptimal/overdosed regimens are found for certain molecularly targeted agents, mostly based on the ancient concept of maximum tolerated dose in oncology. This underlines the lack of comparative effective dose trials before approval. Fortunately, dosing regimens of newly approved molecularly targeted agents is going to evolve with the hope of more convenient and better tolerated treatments. This optimization will bring greater benefit to patients and to healthcare professionals but without addressing the economic issue.