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Drug development in oncology: classical cytotoxics and molecularly targeted agents

Shivaani Kummar1, Martin Gutierrez, James H Doroshow

  • 1Medical Oncology Branch, Center for Cancer Research and Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA.

British Journal of Clinical Pharmacology
|July 18, 2006
PubMed

Insights

Oncological drug development needs faster, more efficient methods. New strategies are required for molecularly targeted agents in early trials, focusing on biomarkers and pharmacogenomics over traditional toxicity measures.

Area of Science:

  • Oncology
  • Pharmacology
  • Biomarkers

Background:

  • Traditional oncological drug development, particularly for cytotoxic chemotherapy, faces challenges in speed and efficiency.
  • Standard approaches for Phase 1 and 2 trials may not be suitable for molecularly targeted agents.
  • Targeted agents often possess a wide therapeutic index and may inhibit tumor growth without cytotoxicity, necessitating alternative evaluation methods.

Purpose of the Study:

  • To highlight the need for improved strategies in oncological drug development.
  • To address the limitations of conventional trial designs for molecularly targeted agents.
  • To emphasize the growing importance of biomarkers and pharmacogenomics in early-phase drug development.

Main Methods:

  • Review of current practices in early-phase oncological clinical trials.
  • Analysis of the characteristics of molecularly targeted agents versus traditional chemotherapy.
  • Discussion of alternative endpoints for evaluating targeted therapies.

Main Results:

  • Conventional dose-finding (maximum tolerability) and efficacy (objective tumor response) metrics may be inadequate for targeted agents.
  • Targeted agents may require evaluation based on pharmacological effects and disease stabilization.
  • There is a clear trend towards integrating biomarkers and pharmacogenomics in early development phases.

Conclusions:

  • Early-phase trial designs must adapt to the unique properties of molecularly targeted agents.
  • Pharmacological effects and disease stabilization are crucial endpoints for targeted therapies.
  • Increased utilization of biomarkers and pharmacogenomics is essential for efficient and effective oncological drug development.

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