Table 1

Selected key issues in assessing a “first in humans” trial of an extract (concentrate) for cancer chemoprevention

1. Single compound, multiple compounds, extract, or food
2. Prior evidence of benefit: epidemiologic, experimental, clinical
3. Prior evidence of toxicity: experimental, clinical
4. Pharmacology
    (a) Extract components: Characterization and reproducibility from batch to batch
    (b) Pharmacokinetics: Dosing and duration issues and similarity between mice and humans
5. Pharmacodynamics
    (a) General markers not necessarily linked to drug mechanism or activity but selected based on carcinogenic progression, either cellular (e.g., proliferation, apoptosis) or molecular (e.g., key signaling pathway alterations).
    (b) Specific markers selected based on mechanistic activity of the agent
    (c) Effect on relevant marker in tissue of interest?
6. Trial Design
    (a) Adequate number of cases.
    (b) Comparability of pre- and post-intervention results.