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Journal of Clinical Oncology, Vol 26, No 14 (May 10), 2008: pp. 2418 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.16.4152
In ReplyEmory University, Winship Cancer Institute, Atlanta, GA We share Dr Kapoor's enthusiasm for the development of natural compound-based chemoprevention approaches to the major tobacco-related cancers.1 However, we would like to note that the data for oral alpha-tocopherol presented in their totality are not quite as positive as he states. In fact, Benner et al2 concluded that despite a significant reduction in micronuclei frequencies in specimens from both the visible lesions and the normal appearing mucosa in patients treated with alpha-tocopherol, there was no significant clinical or histological response associated with this change. As Dr Benner and his collaborators initially cautioned, "micronuclei frequency has not been validated as a biomarker for cancer incidence and consequently, its utility as an intermediate end point for chemoprevention trials is not known."2 This remains the case today. In essence, while promising epidemiologic data continue to suggest that diets high in fruits and vegetables are associated with a reduction in the incidence of head and neck cancer, we have not yet been able to develop definitive prospective trials of potent derivatives of these compounds that have shown meaningful reductions in cancer incidence.3 Ultimately, the development of validated prognostic and predictive markers, such as podoplanin, the molecule investigated by the M.D. Anderson (Houston, TX) team, is critical for the development of novel, natural compound-based chemoprevention approaches that are likely to impact tobacco-related cancers.4 The fact that we have completed two decades of highly-regarded research without managing to validate a single agent as an effective chemopreventive compound against head and neck or lung cancer necessitates this degree of scientific rigor. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Fadlo R. Khuri, Novartis (C), Sanofi-aventis (C) Stock Ownership: None Honoraria: Fadlo R. Khuri, Sanofi-aventis Research Funding: Fadlo R. Khuri, Sanofi-aventis, Genentech, Novartis; Dong M. Shin, Domantis Ltd, UK Expert Testimony: None Other Remuneration: None REFERENCES
1. Khuri FR, Shin DM: Head and neck cancer chemoprevention gets a shot in the arm. J Clin Oncol 26:345-347, 2008 2. Benner SE, Wargovich MJ, Lippman SM, et al: Reduction in oral mucosa micronuclei frequency following alpha-tocopherol treatment of oral leukoplakia. Cancer Epidemiol Biomarkers Prev 3:73-76, 1994[Abstract] 3. Khuri FR, Lee JJ, Lippman SM, et al: Randomized phase III trial of low-dose isotretinoin for prevention of second primary tumors in stage I and II head and neck cancer patients. J Natl Cancer Inst 98:441-450, 2006 4. Kawaguchi H, El-Naggar AK, Papadimitrakopoulou V, et al: Podoplanin: A novel marker for oral cancer risk in patients with oral premalignancy. J Clin Oncol 26:354-360, 2008
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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