Phase I trials of targeted anticancer drugs: a need to refocus
Ernest C Borden1, Afshin Dowlati
1Case Comprehensive Cancer Center, Taussig Cancer Institute R40, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. bordene@ccf.org
Nature Reviews. Drug Discovery
|December 1, 2012
Abstract:
As cancer therapy progresses through the development of molecularly targeted drugs, the focus of Phase I trials needs to shift towards investigating end points that could guide more effective trial design, dosing and choice of tumour setting for Phase II studies.
Insights
Phase I cancer trials need to focus on new endpoints. This will improve the design, dosing, and patient selection for Phase II studies of molecularly targeted drugs.
Area of Science:
- Oncology
- Clinical Pharmacology
- Drug Development
Background:
- Molecularly targeted drugs represent a significant advancement in cancer therapy.
- Current Phase I trial designs may not be optimal for these novel agents.
Purpose of the Study:
- To advocate for a shift in focus for Phase I cancer trials.
- To identify key endpoints that can inform subsequent trial phases.
Main Methods:
- Review of current Phase I trial methodologies.
- Analysis of endpoint utility in guiding Phase II study design.
Main Results:
- Existing endpoints in Phase I trials may not adequately capture the nuances of targeted therapies.
- Specific endpoints are needed to optimize dose selection and patient population for Phase II studies.
Conclusions:
- Phase I trials should prioritize endpoints that facilitate effective Phase II study design.
- Adapting Phase I trial endpoints is crucial for advancing molecularly targeted cancer therapy.
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