How to design a phase I trial of an anticancer botanical Journal Article


Author: Vickers, A. J.
Article Title: How to design a phase I trial of an anticancer botanical
Abstract: Phase I trials are an important part of traditional drug development in oncology. Such trials address two key issues: safety and dose. Currently, there is a dearth of phase I trials of anticancer botanicals. This may result from the apparently widespread view that a history of human use precludes the need for early-phase study. However, the safe use of a botanical by the population at large does not guarantee safety when the botanical is used in combination with other agents in the complex medical setting of oncology. Several cases of unpredictable adverse events have been recorded following the use of botanicals by cancer patients. We propose a simple, robust design for phase I trials of anticancer botanicals. This design incorporates important characteristics of botanical medicines including low toxicity, prior data on a likely safe dose, a limit on the highest dose it is feasible to administer, and the unknown relationship between dose-toxicity and dose-response curves. Two principal design features are the use of predetermined dose levels and the direct measurement of a response endpoint such as survival or immunity. This response end point can be used to determine the optimal dose if toxicity is acceptable at all dose levels. Increasing the use of phase I methodology would ensure a more systematic development of botanicals as anticancer agents. This would likely increase the chance that at least one such agent would be proven to extend lives.
Keywords: survival; cancer chemotherapy; clinical article; controlled study; clinical trial; drug tolerability; review; cytotoxic agent; dose response; drug efficacy; drug safety; research design; drug megadose; methodology; antineoplastic agent; neoplasm; neoplasms; controlled clinical trial; breast cancer; antineoplastic agents, phytogenic; cytotoxicity; drug effect; irinotecan; statistical analysis; drug mechanism; phytotherapy; herbaceous agent; optimal drug dose; maximum tolerated dose; phase 1 clinical trial; immunity; phase i; hypericum perforatum extract; clinical trials, phase i; medicinal plants
Journal Title: Journal of the Society for Integrative Oncology
Volume: 4
Issue: 1
ISSN: 1715-894X
Publisher: BC Decker  
Date Published: 2006-12-01
Start Page: 46
End Page: 51
Language: English
PUBMED: 16737672
PROVIDER: scopus
PMCID: PMC1533748
DOI/URL:
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 4 June 2012" - "Source: Scopus"
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MSK Authors
  1. Andrew J Vickers
    624 Vickers