Related Experiment Video

Updated: Jul 25, 2025

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.1K

Dose Optimization in Oncology Drug Development: The Emerging Role of Pharmacogenomics, Pharmacokinetics, and

Apostolos Papachristos1, Jai Patel2, Maria Vasileiou3

  • 1Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.

Cancers
|June 28, 2023
PubMed

Insights

Optimizing drug dosage in cancer treatment is crucial, especially for targeted therapies. Pharmacological tools can enhance dose selection and improve clinical outcomes.

Area of Science:

  • Oncology
  • Clinical Pharmacology
  • Drug Development

Background:

  • Traditional dose-finding studies in oncology often rely on the Maximum Tolerated Dose (MTD) approach, originally developed for cytotoxic agents.
  • This MTD approach may not be optimal for newer targeted therapies, leading to post-marketing dose adjustments for some anticancer drugs.
  • The FDA's Project Optimus initiative aims to address these limitations by guiding dose optimization in anticancer drug development.

Purpose of the Study:

  • To highlight the limitations of the MTD approach in modern oncology drug development.
  • To emphasize the critical need for dose optimization, particularly for targeted therapies.
  • To explore the role of pharmacological tools in supporting optimal dose selection.

Main Methods:

  • Review of current practices in oncology clinical trial design and dose selection.
  • Analysis of the characteristics of novel therapeutic modalities compared to cytotoxic agents.
  • Identification of relevant pharmacological tools for dose optimization.

Main Results:

  • The MTD approach, while standard, is often insufficient for optimizing doses of novel anticancer agents.
  • Several targeted therapies have required post-marketing dose modifications, indicating suboptimal initial dose selection.
  • Pharmacological tools offer potential solutions for improving dose optimization.

Conclusions:

  • Dose optimization is essential for maximizing the safety and effectiveness of anticancer drugs, especially targeted therapies.
  • Integrating pharmacogenomics, therapeutic drug monitoring, and pharmacodynamics can significantly aid dose optimization throughout clinical development.
  • These tools can improve the likelihood of positive clinical outcomes in cancer patients.
Keywords:
ADCsFDATDMTKIsclinical trialsdose optimizationmonoclonal antibodiespharmacodynamicspharmacogenomicspharmacokinetics

More Related Videos

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice08:57

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice

Published on: October 5, 2017

11.0K
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

8.7K

Related Concept Videos

Nonlinear Pharmacokinetics: Overview01:19

Nonlinear Pharmacokinetics: Overview

Nonlinear or dose-dependent pharmacokinetics is a phenomenon that occurs when the pharmacokinetic parameters of certain drugs deviate from linear pharmacokinetics at higher doses. These drugs do not follow the expected first-order kinetics, where the rate of drug elimination is directly proportional to the drug concentration. Instead, they exhibit a nonlinear relationship, which can be attributed to several factors.
Nonlinearity can arise due to the saturation of plasma protein-binding or...
455
Analysis of Population Pharmacokinetic Data01:12

Analysis of Population Pharmacokinetic Data

Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
301
Pharmacodynamics: Overview and Principles01:21

Pharmacodynamics: Overview and Principles

Pharmacodynamics is a scientific field that delves into drugs' intricate biochemical, cellular, and physiological effects on the human body. The study of pharmacodynamics helps us understand how drugs interact with the body and elicit various responses.
Most drugs' effects result from their interactions with drug receptors or targets within the body. These interactions trigger specific responses at the cellular or systemic level. Drug receptors can be found on the surfaces of cells or...
1.3K
Drug Dosage Regimen: Overview01:15

Drug Dosage Regimen: Overview

A drug dosage regimen describes the specific instructions and schedule for administering a drug to a patient. It considers factors such as drug dosage, frequency, route of administration, and duration of treatment. Designing an appropriate dosage regimen for a patient aims to achieve a target drug concentration at the site of action.
Typically, the starting dose and dosing interval are guided by the manufacturer's recommendations based on clinical trials conducted during and after drug...
3.6K
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
8.1K
Biopharmaceutics and Pharmacokinetics: Overview01:28

Biopharmaceutics and Pharmacokinetics: Overview

Understanding drugs, drug products, and their performance in pharmaceutical science is pivotal. Drugs, whether simple molecules or complex compounds, are designed to interact with the body's biological systems to diagnose, treat, or prevent diseases. Drug products include various delivery systems such as tablets, capsules, injections, and inhalers. The performance of these drug products is gauged by their ability to deliver the active ingredient to the desired site of action at the...
2.1K