Strategy and planning for chemopreventive drug development: Clinical development plans II

Abstract

This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole‐3‐carbinol, perillyl alcohol, phenethyl isothiocyanate, 9‐cis‐retinoic acid, 13‐cis‐retinoic acid, l‐selenomethionine and 1,4‐phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)‐vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs. © 1997 Wiley‐Liss, Inc.

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

“…Considerable interest exists in the use of curcumin as a chemopreventive agent (Kelloff et al, 1994). The results of the analytical determination presented here render it unlikely that curcumin holds any potential in the chemoprevention of hepatic malignancies.…”

“…It exerts cancer chemopreventive efficacy in a wide variety of rodent models of carcinogenesis (Kelloff et al, 1994). In common with several other diet-derived polyphenols, curcumin has low systemic bioavailability (Ireson et al, 2001).…”

Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

“…Curcumin, a well-known dietary pigment derived from the plant Curcuma longa L., has been studied as a chemopreventive agent in several cancer models (25) and entered into Phase I clinical trials for cancer chemoprevention by the National Cancer Institute (26). Previous studies indicated that it efficiently induces antiproliferation and cell death in a variety of tumor cells (27,28) and blocks angiogenic phenotypes in tumor and endothelial cells (16,29).…”

Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine

“…In vitro, curcumin inhibits the growth of cancer cells with an IC 50 value of 20-75μM [6,16]. In rodent models, curcumin has been shown to prevent cancer in the colon, skin, stomach, duodenum, soft palate, tongue, sebaceous glands and breast [9,10,15]. Curcumin undergoes avid metabolism by conjugation (glucuronidation and sulfation) and reduction pathways [7,8].…”