Strategies for identification and clinical evaluation of promising chemopreventive agents.
Strategies for chemopreventative drug development are based on the use of well-characterized agents, intermediate biomarkers correlating to cancer incidence, and suitable cohorts for efficacy studies. Since chemoprevention is applied over the long-term, chemopreventive drugs must have low toxicity. Strategies for enhancing chemopreventive drug efficacy and minimizing toxicity include combinations of drugs with complementary mechanisms and/or synergistic activity; coadministration of drugs to counter the toxicity of the chemopreventive agents; and pursuit of related compounds that retain efficacy with reduced side effects. Because of its slow development, cancer is not a feasible end point for clinical evaluation of chemoprevention, and so intermediate biomarkers that can serve as surrogate end points are crucial. Particularly important biomarkers are the morphometric and cytometric changes defining intraepithelial neoplasia (IEN). Cohorts for chemoprevention trials should have high incidences of the cancer or intermediate biomarker(s) under study within the trial duration.
Kelloff
G J
GJ
Chemoprevention Branch, National Cancer Institute National Institutes of Health Bethesda, Maryland, USA.
Hawk
E T
ET
Crowell
J A
JA
Boone
C W
CW
Nayfield
S G
SG
Perloff
M
M
Steele
V E
VE
Lubet
R A
RA
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D018890:Chemoprevention / Q000379:methods; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*
D014408:Biomarkers, Tumor