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Updated: Jul 5, 2026
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Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Multi-institutional phase I trials of anticancer agents
Afshin Dowlati1, Sudhir Manda, Joseph Gibbons
1Division of Hematology/Oncology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA. afshin.dowlati@case.edu
Summary
Multi-institutional phase I trials increase patient numbers without reducing completion time. However, many targeted agent trials do not establish a maximum-tolerated dose (MTD).
Area of Science:
- Oncology
- Clinical Trials
- Drug Development
Background:
- Phase I trials are crucial for novel anticancer agents.
- Concerns exist regarding multi-institutional trials and optimal biologic dose (OBD) versus maximum-tolerated dose (MTD) endpoints.
- Understanding factors influencing these trials is essential for early drug development.
Purpose of the Study:
- To identify factors associated with multi-institutional phase I studies.
- To determine factors influencing the establishment of the optimal biologic dose (OBD) as an endpoint.
- To address physician concerns regarding early-phase oncology trial design.
Main Methods:
- Systematic review of 463 published phase I trials (1998-2006) from two major clinical cancer journals.
- Data extraction included: number of sites, sponsor, nation, MTD/OBD determination, patient accrual, drug mechanism, accrual time, and tumor type.
- Statistical analysis to compare single-institution vs. multi-institutional trials and identify influencing factors.
Main Results:
- 56% of trials were single-institution; 30% reported accrual time.
- Multi-institutional trials enrolled more patients but had similar accrual times compared to single-institution trials.
- NIH-sponsored trials enrolled fewer patients than pharmaceutical-sponsored trials; 99% of cytotoxic trials determined MTD, vs. 64% for targeted agents.
Conclusions:
- Multi-institutional phase I studies enhance patient accrual without negatively impacting study completion time.
- A significant proportion (one-third) of targeted agent trials did not establish a maximum-tolerated dose (MTD).
- These findings inform strategies for optimizing early-phase oncology trial design and endpoint selection.
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