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What are the reasons for negative phase III trials of molecular-target-based drugs?

Nagahiro Saijo1

  • 1National Cancer Center Hospital East, Kashiwa-shi, Chiba 277-8577, Japan. nsaijo@east.ncc.go.jp

Cancer Science
|October 27, 2004
PubMed

Insights

Molecular-target-based cancer therapy shows promise, but many phase III trials yield negative results. This review clarifies therapy value and discusses reasons for trial failures, emphasizing proof-of-principle studies.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Molecular-biological studies are revolutionizing cancer diagnosis and treatment.
  • Target-based drug discovery focuses on specific mechanisms of action.
  • Classical drug-receptor theory underpins understanding of drug-target interactions.

Purpose of the Study:

  • To clarify the clinical value of molecular-target-based therapy.
  • To discuss reasons for negative outcomes in phase III clinical trials.
  • To emphasize the importance of proof-of-principle studies.

Main Methods:

  • Review of molecular-biological studies in cancer.
  • Analysis of target-based drug discovery principles.
  • Examination of clinical trial data, including phase III trials.

Main Results:

  • Some effective target-based drugs induce apoptosis, despite being classified as cytostatic.
  • Numerous phase III trials have been conducted for target-based drugs.
  • The majority of phase III trials for target-based drugs have yielded negative results.

Conclusions:

  • Clarifying the value of molecular-target-based therapy is crucial.
  • Understanding the reasons for negative phase III trial results is essential for future drug development.
  • Proof-of-principle studies are vital throughout preclinical and clinical development.

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