Optimized Dosing: The Next Step in Precision Medicine in Non-Small-Cell Lung Cancer

Abstract

In oncology, and especially in the treatment of non-small-cell lung cancer (NSCLC), dose optimization is often a neglected part of precision medicine. Many drugs are still being administered in "one dose fits all" regimens or based on parameters that are often only minor determinants for systemic exposure. These dosing approaches often introduce additional pharmacokinetic variability and do not add to treatment outcomes. Fortunately, pharmacological knowledge is increasing, providing valuable information regarding the potential of, for example, therapeutic drug monitoring. This article focuses on the evidence for the most promising and easily implemented optimized dosing approaches for the small-molecule inhibitors, chemotherapeutic agents, and monoclonal antibodies as treatment options currently approved for NSCLC. Despite limitations such as investigations having been conducted in oncological diseases other than NSCLC or the retrospective origin of many analyses, an alternative dosing regimen could be beneficial for treatment outcomes, prescriber convenience, or financial burden on healthcare systems. This review of the literature provides recommendations on the implementation of dose optimization and advice regarding promising strategies that deserve further research in NSCLC.

Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer

“…Based on the Global Cancer Statistics of 2020, lung cancer ranks the second most frequently diagnosed cancer (11.4% of total cases) and is the leading cause of cancer-related death (18% of total cancer deaths)[ 1 ]. At present, therapeutic regimens for lung cancer include surgery, chemotherapy, immunotherapy, and targeted therapy[ 2 ]. Despite the continuous refinement of treatment options, the 5-year survival rate still remains below 20%[ 3 ].…”

Pharmacokinetically guided dosing to improve the efficacy of brigatinib in non‐small cell lung cancer patients

“…In the current age of precision medicine, many drugs are not used optimally. 4 It is known that the outcomes of clinical studies supporting these dosing regimens do not reflect the real-world situation. For example, due to different treatment adherence, evasion of drug-drug interactions, or exclusion of patients with certain comorbidities, potentially causing changes in pharmacokinetics or treatment response.…”

Ritonavir-Boosted Exposure of Kinase Inhibitors: an Open Label, Cross-over Pharmacokinetic Proof-of-Concept Trial with Erlotinib

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