Related Experiment Video

Updated: Sep 20, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Clinical trial design for target specific anticancer agents

Ronald Hoekstra1, Jaap Verweij, Ferry A L M Eskens

  • 1Department of Medical Oncology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. R.Hoekstra.1@erasmusmc.nl

Investigational New Drugs
|August 2, 2003
PubMed

Insights

New targeted anticancer agents are cytostatic, not cytotoxic, requiring adapted clinical trial designs. Phase I and II studies need modification to accurately assess efficacy and safety of these novel therapies.

Area of Science:

  • Oncology
  • Clinical Trial Design
  • Pharmacology

Background:

  • Numerous novel anticancer agents target specific cellular processes involved in cancer.
  • These agents primarily exhibit cytostatic (growth inhibition) rather than cytotoxic (cell death) effects.
  • Target-specific agents are anticipated to have improved toxicity profiles compared to traditional chemotherapies.

Purpose of the Study:

  • To discuss challenges in developing clinical trials for new target-specific anticancer agents.
  • To propose adaptations for Phase I and II study designs based on the cytostatic nature of these drugs.
  • To integrate these adaptations with existing concepts for cytotoxic and cytostatic agent trial design.

Main Methods:

  • Review of current practices in Phase I and II clinical trial design for anticancer agents.
  • Analysis of the impact of cytostatic mechanisms on toxicity and efficacy assessment.
  • Conceptual framework development for adapting trial designs for target-specific agents.

Main Results:

  • Current Phase I/II trial designs, focused on dose-limiting toxicity and tumor regression, may be inadequate for cytostatic agents.
  • Adaptations are necessary to appropriately evaluate the efficacy (growth inhibition) and safety of target-specific therapies.
  • Distinguishing between cytotoxic and cytostatic agents, while useful, can be an oversimplification requiring nuanced trial approaches.

Conclusions:

  • Clinical trial designs for novel anticancer agents must evolve to accommodate their cytostatic mechanisms and favorable toxicity profiles.
  • Modified Phase I/II studies are crucial for accurately assessing the therapeutic potential of target-specific anticancer drugs.
  • Future research should focus on refining trial methodologies to better suit the unique characteristics of emerging cancer therapies.

More Related Videos

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

Assessing Specificity of Anticancer Drugs In Vitro09:39

Assessing Specificity of Anticancer Drugs In Vitro

Published on: March 23, 2016

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...