© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 15, 1281-1287,
August 4, 1999
© 1999 Oxford University Press
COMMENTARY |
Anticancer Agents Targeting Signaling Molecules and Cancer Cell Environment: Challenges for Drug Development?
Affiliations of authors: K. A. Gelmon, British Columbia Cancer Agency, Vancouver, BC, Canada; E. A. Eisenhauer, National Cancer Institute of Canada Clinical Trials Group, Kingston, ON; A. L. Harris, University of Oxford, U.K.; M. J. Ratain, The University of Chicago, IL; P. Workman, Cancer Research Campaign Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, U.K.
Correspondence to: Karen A. Gelmon, M.D., British Columbia Cancer Agency Vancouver Cancer Centre, 600 W. 10th Ave., Vancouver, BC V5Z 4E6, Canada (e-mail: kgelmon@bccancer.bc.ca).
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INTRODUCTION |
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The focus of drug development has moved from cytotoxic compounds identified by screening to therapies that act at specific molecular targets. Although some of these agents may cause visible tumor reduction and may be adequately evaluated by standard oncology drug development methods, other novel therapies may not be amenable to our current practices. Consequently, our concepts of drug development must evolve and address various questions. How should we approach the preclinical development of these agents? Which laboratory experiments are critical prior to studying these new agents in the clinic? What phase I design strategies are appropriate? Agents that target specific molecules may not cause toxicity at effective doses and, therefore, phase I concepts such as maximum tolerated dose (MTD) may not be relevant. What phase II designs suit these agents? Drugs that have a cytostatic effect may be overlooked if tumor response is required as a selection criteria. Phase II
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PRECLINICAL ASSESSMENT |
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PHASE I TRIAL DESIGN |
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PHASE II AND BEYOND: ASSESSMENT OF EFFICACY |
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LESSONS FROM NONONCOLOGY DRUGS |
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CONCLUSION |
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NOTES |
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REFERENCES |
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