From Dose-Finding to Dose-Optimization in Early-Phase oncology clinical trials

Area of Science:

• Oncology
• Clinical Pharmacology

Background:

• Traditional Phase I oncology trial designs, like the 3+3 method, prioritize safety but can lead to suboptimal dosing.
• These methods often do not accommodate the complex pharmacokinetics and pharmacodynamics of novel cancer therapies, including targeted agents and immunotherapies.

Purpose of the Study:

• To review current dose optimization strategies in Phase I oncology trials.
• To highlight the limitations of traditional dose-escalation methods and advocate for contemporary, patient-centered approaches.

Main Methods:

• Review of existing literature on Phase I oncology trial designs.
• Discussion of innovative strategies incorporating biomarkers, pharmacokinetic/pharmacodynamic profiling, and patient-reported outcomes.

Main Results:

• Traditional methods may result in prolonged exposure to ineffective or toxic doses.
• Contemporary approaches enhance precision in dose selection and support individualized cancer care.

Conclusions:

• Distinguishing between dose-finding and dose optimization is essential for effective early-phase trials.
• Integrating patient perspectives and pharmacologic insights into trial design can expedite the delivery of tailored cancer therapies.