Risks and Benefits of Phase 1 Clinical Trials Evaluating New Anticancer Agents
A Case for More Innovation
- Eric X. Chen, MD, PhD;
- Ian F. Tannock, MD, PhD
- Author Affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital and University of Toronto, Toronto, Ontario.
- Corresponding Author: Ian F. Tannock, MD, PhD, Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Toronto, Ontario, Canada M5G 2M9 (ian.tannock{at}uhn.on.ca).
Since this article does not have an abstract, we have provided the first 150 words of the full text.
The development of new anticancer agents follows a well-established paradigm that progresses sequentially from phase 1 through phase 3 clinical trials. Phase 1 clinical trials are first in human studies of investigational agents and enroll patients with advanced or refractory disease for whom no standard options exist. The starting dose is usually about one tenth of the lethal dose in animals that have been used for preclinical studies of toxicity. Cohorts of 3 to 6 patients are treated at each dose level, and the dose escalation in most studies involves higher escalation steps with decreasing relative increments.1 Dose escalation within the same patient is not permitted in most studies because of the desire to evaluate patients for cumulative or delayed toxicity at lower doses. The primary objectives of phase 1 studies are to evaluate the safety and tolerability of new agents and to recommend doses and schedules for phase …
