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Updated: Feb 22, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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Clinical Pharmacology Tools and Evaluations to Facilitate Comprehensive Dose Finding in Oncology: A Continuous

Julie M Bullock1, Tiffany Lin1, Sanela Bilic1

  • 1D3 Medicine, a Certara USA Company, Parsippany, NJ, USA.

Journal of Clinical Pharmacology
|September 19, 2017
PubMed

Insights

Developing targeted cancer therapies requires shifting from toxicity-guided dosing to target activity. This involves integrated pharmacokinetic and pharmacodynamic assessments for robust risk-benefit analysis and optimal dose selection.

Area of Science:

  • Oncology
  • Clinical Pharmacology
  • Drug Development

Background:

  • Targeted therapies are crucial in cancer treatment.
  • Traditional cytotoxic drug development relied on toxicity-guided dose finding (maximum tolerated dose).
  • This paradigm needs refinement for targeted agents, focusing on target activity.

Purpose of the Study:

  • To advocate for an integrated approach in targeted therapy development.
  • To emphasize the shift from toxicity-driven to target activity-driven dose selection.
  • To highlight the importance of pharmacometric analyses for risk-benefit assessment.

Main Methods:

  • Collecting pharmacokinetic (PK) and pharmacodynamic (PD) samples throughout clinical development.
  • Identifying PK covariates influencing drug exposure.
  • Correlating exposure with safety and efficacy markers using pharmacometric analyses.
  • Considering food effects for oral agents' administration and outcomes.

Main Results:

  • An integrated approach is essential for characterizing drug risk-benefit.
  • Pharmacometric modeling aids in robust risk-benefit assessment and dose establishment.
  • PK/PD assessments are key to understanding drug activity and safety profiles.

Conclusions:

  • Model-based drug development provides a robust decision-making tool.
  • Clinical pharmacology assessments are vital for successful oncology drug development.
  • Optimizing dose selection based on target activity and PK/PD data improves risk-benefit.
Keywords:
clinical pharmacologydose justificationexposure-responsefood effectoncologyrisk-benefit

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