On precision dosing of oral small molecule drugs in oncology

Personalization of oral small molecule anticancer drug doses based on individual patient blood drug levels, also known as therapeutic drug monitoring (TDM), has the potential to significantly improve the effectiveness of treatment by maximizing drug efficacy and minimize toxicity. However, this option has not yet been widely embraced by the oncology community. Some reasons for this include increased logistical complexity of dose individualization, the lack of clinical laboratories that measure small molecule drug concentrations in support of patient care, and the lack of reimbursement of costs. However, the main obstacle may be the lack of studies clearly demonstrating that monitoring of oral small molecule anticancer drug levels actually improves clinical outcomes. Without unequivocal evidence in support of TDM-guided dose individualization, especially demonstration of improved survival with TDM in randomized controlled trials, wide acceptance of this approach by oncologists and reimbursement by insurance companies is unlikely, and patients may continue to suffer as a result of receiving incorrect drug doses. This article reviews the current status of TDM of oral small molecule drugs in oncology and intends to provide strategic insights into the design of studies for evaluating the utility of TDM in this clinical context.