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  • Review Article
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Primer: first do no harm—when is it appropriate to plan a cancer prevention clinical trial?

Nature Clinical Practice Oncology volume 5, pages 348–356 (2008)Cite this article

Abstract

Abundant preclinical and clinical data suggest that cancer is a preventable disease; however, few, if any, of the medical interventions available are completely without adverse effects or risk to the patient. This statement is especially true with regard to phenotypically healthy but high-risk populations. Balancing the risks from interventions with the risk of future life-threatening disease is particularly challenging because no standardized methodologies to perform such calculations exist. It is critical, therefore, to establish a framework for determining when interventions show sufficient promise of efficacy and sufficient safety to justify their testing in clinical trials. Systematic review of all available preclinical, epidemiological, and clinical data, along with a mechanistic understanding of the biology of the disease under study, is mandatory before clinical trials are embarked upon. This Review identifies the issues that are critical for decision-making when clinical trials in human beings are being contemplated and provides a framework that can be applied in making these decisions.

Key Points

  • Selection of agents for cancer prevention clinical trials requires a thorough understanding of the potential efficacy and toxic effects associated with specific agents

  • Evidence of effectiveness at cancer prevention comes from investigation of mechanisms, in vitro and animal in vivo experiments, epidemiological case–control and cohort studies, and clinical trials (including both early-phase cancer prevention trials and secondary end point analysis of trials performed for other indications)

  • The risk:benefit balance can be shifted towards benefit by the development of trials in appropriately high-risk cohorts and use of low-toxicity regional, combination, or intermittent drug delivery regimens whenever possible

  • Understanding the molecular mechanisms and the temporal sequence of events that result in carcinogenesis is critical to the choice of agents and the design of prevention trials

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Author notes

  1. Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, Room 2132, Bethesda, MD 20892, USA szaboe@mail.nih.gov

Authors and Affiliations

  1. E Szabo is Chief of the Lung and Upper Aerodigestive Cancer Research Group at the National Cancer Institute, Bethesda, MD, USA.,

    Eva Szabo

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  1. Eva Szabo
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Szabo, E. Primer: first do no harm—when is it appropriate to plan a cancer prevention clinical trial?. Nat Rev Clin Oncol 5, 348–356 (2008). https://doi.org/10.1038/ncponc1123

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