TY - JOUR
T1 - Surrogate endpoint biomarkers for cervical cancer chemoprevention trials
AU - Ruffin, Mack T.
AU - Ogaily, Mohammed S.
AU - Johnston, Carolyn M.
AU - Gregoire, Lucie
AU - Lancaster, Wayne D.
AU - Brenner, Dean E.
PY - 1995
Y1 - 1995
N2 - Cervical intraepithelia neoplasia (CIN) represents a spectrum of epithelial changes that provide an excellent model for developing chemopreventive interventions for cervical cancer. Possible drug effect surrogate endpoint biomarkers are dependent on the agent under investigation. Published and preliminary clinical reports suggest retinoids and carotenoids are effective chemopreventive agents for CIN. Determination of plasma and tissue pharmacology of these agents and their metabolites could serve as drug effect intermediate endpoints. In addition, retinoic acid receptors could serve as both drug and biological effect intermediate endpoints. Possible biological effect surrogate endpoint biomarkers include cytomorphological parameters, proliferation markers, genomic markers, regulatory markers, and differentiation. Given the demonstrated causality of human papillomavirus (HPV) for cervical cancer, establishing the relationship to HPV will be an essential component of any biological intermediate endpoint biomarker. The pathologic effect surrogate endpoint biomarker for cervical cancer is CIN, used clinically for years. The desired effect for chemopreventive trials is complete regression or prevention of progression. In planning chemopreventive trials, investigators need to consider spontaneous regression rates, the subjective nature of detecting CIN, and the impact of biopsy on regression. If intermediate endpoint biomarkers that met the above criteria were available for cervical cancer, then new chemopreventive agents could be rapidly explored. The efficacy of these new agents could be determined with a moderate number of subjects exposed to minimal risk over an acceptable amount of time. The impacts on health care for women would be significant.
AB - Cervical intraepithelia neoplasia (CIN) represents a spectrum of epithelial changes that provide an excellent model for developing chemopreventive interventions for cervical cancer. Possible drug effect surrogate endpoint biomarkers are dependent on the agent under investigation. Published and preliminary clinical reports suggest retinoids and carotenoids are effective chemopreventive agents for CIN. Determination of plasma and tissue pharmacology of these agents and their metabolites could serve as drug effect intermediate endpoints. In addition, retinoic acid receptors could serve as both drug and biological effect intermediate endpoints. Possible biological effect surrogate endpoint biomarkers include cytomorphological parameters, proliferation markers, genomic markers, regulatory markers, and differentiation. Given the demonstrated causality of human papillomavirus (HPV) for cervical cancer, establishing the relationship to HPV will be an essential component of any biological intermediate endpoint biomarker. The pathologic effect surrogate endpoint biomarker for cervical cancer is CIN, used clinically for years. The desired effect for chemopreventive trials is complete regression or prevention of progression. In planning chemopreventive trials, investigators need to consider spontaneous regression rates, the subjective nature of detecting CIN, and the impact of biopsy on regression. If intermediate endpoint biomarkers that met the above criteria were available for cervical cancer, then new chemopreventive agents could be rapidly explored. The efficacy of these new agents could be determined with a moderate number of subjects exposed to minimal risk over an acceptable amount of time. The impacts on health care for women would be significant.
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U2 - 10.1002/jcb.240590915
DO - 10.1002/jcb.240590915
M3 - Article
C2 - 8747385
AN - SCOPUS:0029445536
SN - 0730-2312
VL - 59
SP - 113
EP - 124
JO - Journal of cellular biochemistry
JF - Journal of cellular biochemistry
IS - 23 S
ER -