FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 328:15-20 January 7, 1993 Number 1 Next

	Full Text Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background High-dose isotretinoin therapy has been determined to be an effective treatment for leukoplakia. However, a high rate of relapses and toxic reactions led us to conduct a trial of a much lower dose of isotretinoin in the hope of maintaining a response and limiting toxicity.

Methods In the first phase of the study, 70 patients with leukoplakia underwent induction therapy with a high dose of isotretinoin (1.5 mg per kilogram of body weight per day) for three months; in the second phase, patients with responses or stable lesions were randomly assigned to maintenance therapy with either beta carotene (30 mg per day) or a low dose of isotretinoin (0.5 mg per kilogram per day) for nine months.

Results In the first phase, the rate of response to high-dose induction therapy in the 66 patients who could be evaluated was 55 percent (36 patients). The lesions of seven patients progressed, and therefore they did not participate in the second phase of the trial. Of the 59 patients included in the second phase, 33 were assigned to beta carotene therapy and 26 to low-dose isotretinoin therapy; these two groups did not differ significantly in prognostic factors. Of the 53 patients who could be evaluated, 22 in the low-dose isotretinoin group and 13 in the beta carotene group responded to maintenance therapy or continued to have stable lesions (92 percent vs. 45 percent, P<0.001). In situ carcinoma developed in one patient in each group, and invasive squamous-cell carcinoma in five patients in the beta carotene group. Toxicity was generally mild, though greater in the group given low-dose isotretinoin therapy.

Conclusions When preceded by high-dose induction therapy, low-dose isotretinoin therapy was significantly more active against leukoplakia than beta carotene and was easily tolerated.

Source Information

From the Departments of Medical Oncology (S.M.L., W.K.H.), Pathology (J.G.B.), Dental Oncology (B.B.T., J.W.M.), Head and Neck Surgery (R.S.W., H.G.), and Biomathematics (J.J.L.), University of Texas M.D. Anderson Cancer Center; and the Department of Oral Diagnostic Sciences, University of Texas Health Science Center Dental Branch (G.L.H.) -- both in Houston.

Address reprint requests to Dr. Lippman at the Department of Medical Oncology, Box 80, University of Texas M.D., anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

Full Text of this Article

This article has been cited by other articles:

• Shin, D. M. (2009). Oral Cancer Prevention Advances with a Translational Trial of Green Tea. Cancer Prevention Research 2: 919-921 [Abstract] [Full Text]  
• Tsao, A. S., Liu, D., Martin, J., Tang, X.-m., Lee, J. J., El-Naggar, A. K., Wistuba, I., Culotta, K. S., Mao, L., Gillenwater, A., Sagesaka, Y. M., Hong, W. K., Papadimitrakopoulou, V. (2009). Phase II Randomized, Placebo-Controlled Trial of Green Tea Extract in Patients with High-Risk Oral Premalignant Lesions. Cancer Prevention Research 2: 931-941 [Abstract] [Full Text]  
• Lippman, S. M., Hawk, E. T. (2009). Cancer Prevention: From 1727 to Milestones of the Past 100 Years. Cancer Res. 69: 5269-5284 [Abstract] [Full Text]  
• Amin, A.R.M. R., Kucuk, O., Khuri, F. R., Shin, D. M. (2009). Perspectives for Cancer Prevention With Natural Compounds. JCO 27: 2712-2725 [Abstract] [Full Text]  
• Lippman, S. M. (2009). Cancer Prevention Research: Back to the Future. Cancer Prevention Research 2: 503-513 [Full Text]  
• Kelly, K., Kittelson, J., Franklin, W. A., Kennedy, T. C., Klein, C. E., Keith, R. L., Dempsey, E. C., Lewis, M., Jackson, M. K., Hirsch, F. R., Bunn, P. A., Miller, Y. E. (2009). A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without {alpha} Tocopherol or Observation in Subjects at High Risk for Lung Cancer. Cancer Prevention Research 2: 440-449 [Abstract] [Full Text]  
• Papadimitrakopoulou, V. A., Lee, J. J., William, W. N. Jr, Martin, J. W., Thomas, M., Kim, E. S., Khuri, F. R., Shin, D. M., Feng, L., Hong, W. K., Lippman, S. M. (2009). Randomized Trial of 13-cis Retinoic Acid Compared With Retinyl Palmitate With or Without Beta-Carotene in Oral Premalignancy. JCO 27: 599-604 [Abstract] [Full Text]  
• Papadimitrakopoulou, V., Izzo, J. G., Liu, D. D., Myers, J., Ceron, T. L., Lewin, J., William, W. N. Jr., Atwell, A., Lee, J. J., Gillenwater, A., El-Naggar, A., Wu, X., Lippman, S. M., Hittelman, W. N., Hong, W. K. (2009). Cyclin D1 and Cancer Development in Laryngeal Premalignancy Patients. Cancer Prevention Research 2: 14-21 [Abstract] [Full Text]  
• William, W. N. Jr., Lee, J. J., Lippman, S. M., Martin, J. W., Chakravarti, N., Tran, H. T., Sabichi, A. L., Kim, E. S., Feng, L., Lotan, R., Papadimitrakopoulou, V. A. (2009). High-Dose Fenretinide in Oral Leukoplakia. Cancer Prevention Research 2: 22-26 [Abstract] [Full Text]  
• Mallery, S. R., Zwick, J. C., Pei, P., Tong, M., Larsen, P. E., Shumway, B. S., Lu, B., Fields, H. W., Mumper, R. J., Stoner, G. D. (2008). Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions. Cancer Res. 68: 4945-4957 [Abstract] [Full Text]  
• Shumway, B. S., Kresty, L. A., Larsen, P. E., Zwick, J. C., Lu, B., Fields, H. W., Mumper, R. J., Stoner, G. D., Mallery, S. R. (2008). Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions. Clin. Cancer Res. 14: 2421-2430 [Abstract] [Full Text]  
• Papadimitrakopoulou, V. A., William, W. N. Jr., Dannenberg, A. J., Lippman, S. M., Lee, J. J., Ondrey, F. G., Peterson, D. E., Feng, L., Atwell, A., El-Naggar, A. K., Nathan, C.-A., Helman, J. I., Du, B., Yueh, B., Boyle, J. O. (2008). Pilot Randomized Phase II Study of Celecoxib in Oral Premalignant Lesions. Clin. Cancer Res. 14: 2095-2101 [Abstract] [Full Text]  
• Visus, C., Ito, D., Amoscato, A., Maciejewska-Franczak, M., Abdelsalem, A., Dhir, R., Shin, D. M., Donnenberg, V. S., Whiteside, T. L., DeLeo, A. B. (2007). Identification of Human Aldehyde Dehydrogenase 1 Family Member A1 as a Novel CD8+ T-Cell Defined Tumor Antigen in Squamous Cell Carcinoma of the Head and Neck. Cancer Res. 67: 10538-10545 [Abstract] [Full Text]  
• Chen, X.-c., Wang, R., Zhao, X., Wei, Y.-q., Hu, M., Wang, Y.-s., Zhang, X.-w., Zhang, R., Zhang, L., Yao, B., Wang, L., Jia, Y.-q., Zeng, T.-t., Yang, J.-l., Tian, L., Kan, B., Lin, X.-j., Lei, S., Deng, H.-x., Wen, Y.-j., Mao, Y.-q., Li, J. (2006). Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs. Carcinogenesis 27: 2434-2441 [Abstract] [Full Text]  
• Lippman, S. M., Lee, J. J., Martin, J. W., El-Naggar, A. K., Xu, X., Shin, D. M., Thomas, M., Mao, L., Fritsche, H. A. Jr., Zhou, X., Papadimitrakopoulou, V., Khuri, F. R., Tran, H., Clayman, G. L., Hittelman, W. N., Hong, W. K., Lotan, R. (2006). Fenretinide Activity in Retinoid-Resistant Oral Leukoplakia.. Clin. Cancer Res. 12: 3109-3114 [Abstract] [Full Text]  
• Lippman, S. M., Lee, J. J. (2006). Reducing the "Risk" of Chemoprevention: Defining and Targeting High Risk--2005 AACR Cancer Research and Prevention Foundation Award Lecture.. Cancer Res. 66: 2893-2903 [Abstract] [Full Text]  
• Choe, M. S., Zhang, X., Shin, H. J. C., Shin, D. M., Chen, Z. (2005). Interaction between epidermal growth factor receptor- and cyclooxygenase 2-mediated pathways and its implications for the chemoprevention of head and neck cancer. Molecular Cancer Therapeutics 4: 1448-1455 [Abstract] [Full Text]  
• Seixas-Silva, J. A. Jr, Richards, T., Khuri, F. R., Wieand, H. S., Kim, E., Murphy, B., Francisco, M., Hong, W. K., Shin, D. M. (2005). Phase 2 Bioadjuvant Study of Interferon Alfa-2a, Isotretinoin, and Vitamin E in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Long-term Follow-up. Arch Otolaryngol Head Neck Surg 131: 304-307 [Abstract] [Full Text]  
• Perry, C. F., Stevens, M., Rabie, I., Yarker, M.-E., Cochrane, J., Perry, E., Traficante, R., Coman, W. (2005). Chemoprevention of Head and Neck Cancer With Retinoids: A Negative Result. Arch Otolaryngol Head Neck Surg 131: 198-203 [Abstract] [Full Text]  
• Lippman, S. M., Sudbo, J., Hong, W. K. (2005). Oral Cancer Prevention and the Evolution of Molecular-Targeted Drug Development. JCO 23: 346-356 [Abstract] [Full Text]  
• Sudbo, J. (2004). Novel Management of Oral Cancer: A Paradigm of Predictive Oncology. Clin Med Res 2: 233-242 [Abstract] [Full Text]  
• Rhee, J. C., Khuri, F. R., Shin, D. M. (2004). Advances in Chemoprevention of Head and Neck Cancer. The Oncologist 9: 302-311 [Abstract] [Full Text]  
• Tsao, A. S., Kim, E. S., Hong, W. K. (2004). Chemoprevention of Cancer. CA Cancer J Clin 54: 150-180 [Abstract] [Full Text]  
• Alberts, D., Ranger-Moore, J., Einspahr, J., Saboda, K., Bozzo, P., Liu, Y., Xu, X.-c., Lotan, R., Warneke, J., Salasche, S., Stratton, S., Levine, N., Goldman, R., Islas, M., Duckett, L., Thompson, D., Bartels, P. (2004). Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin. Clin. Cancer Res. 10: 1875-1880 [Abstract] [Full Text]  
• Rudin, C. M., Cohen, E. E.W., Papadimitrakopoulou, V. A., Silverman, S. Jr, Recant, W., El-Naggar, A. K., Stenson, K., Lippman, S. M., Hong, W. K., Vokes, E. E. (2003). An Attenuated Adenovirus, ONYX-015, As Mouthwash Therapy for Premalignant Oral Dysplasia. JCO 21: 4546-4552 [Abstract] [Full Text]  
• Sabichi, A. L., Demierre, M.-F., Hawk, E. T., Lerman, C. E., Lippman, S. M. (2003). Frontiers in Cancer Prevention Research. Cancer Res. 63: 5649-5655 [Full Text]  
• Lango, M., Wentzel, A. L., Song, J. I., Xi, S., Johnson, D. E., Lamph, W. W., Miller, L., Grandis, J. R. (2003). Responsiveness to the Retinoic Acid Receptor-selective Retinoid LGD1550 Correlates with Abrogation of Transforming Growth Factor {alpha}/Epidermal Growth Factor Receptor Autocrine Signaling in Head and Neck Squamous Carcinoma Cells. Clin. Cancer Res. 9: 4205-4213 [Abstract] [Full Text]  
• Kakizoe, T. (2003). Chemoprevention of Cancer - Focusing on Clinical Trials. Jpn J Clin Oncol 33: 421-442 [Abstract] [Full Text]  
• Armstrong, W. B., Taylor, T. H., Meyskens, F. L. Jr. (2003). Point: Surrogate End Point Biomarkers Are Likely To Be Limited in Their Usefulness in the Development of Cancer Chemoprevention Agents against Sporadic Cancers. Cancer Epidemiol. Biomarkers Prev. 12: 589-592 [Full Text]  
• Soprano, K. J., Soprano, D. R. (2002). Retinoic Acid Receptors and Cancer. J. Nutr. 132: 3809S-3813 [Abstract] [Full Text]  
• Lippman, S. M., Hong, W. K. (2002). Cancer Prevention Science and Practice. Cancer Res. 62: 5119-5125 [Full Text]  
• Lippman, S. M., Ki Hong, W. (2002). Cancer Prevention by Delay : Commentary re: J. A. O'Shaughnessy et al., Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development. Clin. Cancer Res., 8: 314-346, 2002.. Clin. Cancer Res. 8: 305-313 [Full Text]  
• O'Shaughnessy, J. A., Kelloff, G. J., Gordon, G. B., Dannenberg, A. J., Hong, W. K., Fabian, C. J., Sigman, C. C., Bertagnolli, M. M., Stratton, S. P., Lam, S., Nelson, W. G., Meyskens, F. L., Alberts, D. S., Follen, M., Rustgi, A. K., Papadimitrakopoulou, V., Scardino, P. T., Gazdar, A. F., Wattenberg, L. W., Sporn, M. B., Sakr, W. A., Lippman, S. M., Von Hoff, D. D. (2002). Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development : Recommendations of the American Association for Cancer Research Task Force on the Treatment and Prevention of Intraepithelial Neoplasia. Clin. Cancer Res. 8: 314-346 [Abstract] [Full Text]  
• Young, R. C., Wilson, C. M. (2002). Cancer Prevention: Past, Present, and Future. Clin. Cancer Res. 8: 11-16 [Abstract] [Full Text]  
• Follen, M., Atkinson, E. N., Schottenfeld, D., Malpica, A., West, L., Lippman, S., Zou, C., Hittelman, W. N., Lotan, R., Hong, W. K. (2001). A Randomized Clinical Trial of 4-Hydroxyphenylretinamide for High-Grade Squamous Intraepithelial Lesions of the Cervix. Clin. Cancer Res. 7: 3356-3365 [Abstract] [Full Text]  
• Antman, K., Benson, M. C., Chabot, J., Cobrinik, D., Grann, V. R., Jacobson, J. S., Joe, A. K., Katz, A. E., Kelly, K., Neugut, A. I., Russo, D., Tiersten, A., Weinstein, I. B. (2001). Complementary and Alternative Medicine: The Role of the Cancer Center. JCO 19: 55s-60 [Full Text]  
• Lippman, S. M., Spitz, M. R. (2001). Lung Cancer Chemoprevention: An Integrated Approach. JCO 19: 74s-82 [Abstract] [Full Text]  
• Shin, D. M., Khuri, F. R., Murphy, B., Garden, A. S., Clayman, G., Francisco, M., Liu, D., Glisson, B. S., Ginsberg, L., Papadimitrakopoulou, V., Myers, J., Morrison, W., Gillenwater, A., Ang, K. K., Lippman, S. M., Goepfert, H., Hong, W. K. (2001). Combined Interferon-Alfa, 13-cis-Retinoic Acid, and Alpha-Tocopherol in Locally Advanced Head and Neck Squamous Cell Carcinoma: Novel Bioadjuvant Phase II Trial. JCO 19: 3010-3017 [Abstract] [Full Text]  
• Khuri, F. R., Rigas, J. R., Figlin, R. A., Gralla, R. J., Shin, D. M., Munden, R., Fox, N., Huyghe, M. R., Kean, Y., Reich, S. D., Hong, W. K. (2001). Multi-Institutional Phase I/II Trial of Oral Bexarotene in Combination With Cisplatin and Vinorelbine in Previously Untreated Patients With Advanced Non-Small-Cell Lung Cancer. JCO 19: 2626-2637 [Abstract] [Full Text]  
• Lippman, S. M., Lee, J. J., Karp, D. D., Vokes, E. E., Benner, S. E., Goodman, G. E., Khuri, F. R., Marks, R., Winn, R. J., Fry, W., Graziano, S. L., Gandara, D. R., Okawara, G., Woodhouse, C. L., Williams, B., Perez, C., Kim, H. W., Lotan, R., Roth, J. A., Hong, W. K. (2001). Randomized Phase III Intergroup Trial of Isotretinoin to Prevent Second Primary Tumors in Stage I Non-Small-Cell Lung Cancer. JNCI J Natl Cancer Inst 93: 605-618 [Abstract] [Full Text]  
• Lippman, S. M., Matrisian, L. M. (2000). Protease Inhibitors in Oral Carcinogenesis and Chemoprevention. Clin. Cancer Res. 6: 4599-4603 [Full Text]  
• Thaller, C., Shalev, M., Frolov, A., Eichele, G., Thompson, T. C., Williams, R. H., Dillioglugil, O., Kadmon, D. (2000). Fenretinide Therapy in Prostate Cancer: Effects on Tissue and Serum Retinoid Concentration. JCO 18: 3804-3808 [Abstract] [Full Text]  
• Hong, W. K., Spitz, M. R., Lippman, S. M. (2000). Cancer Chemoprevention in the 21st Century: Genetics, Risk Modeling, and Molecular Targets. JCO 18: 9s-18 [Full Text]  
• Shalev, M., Thompson, T. C., Frolov, A., Lippman, S. M., Hong, W. K., Fritsche, H., Kadmon, D. (2000). Effect of 13-cis-Retinoic Acid on Serum Prostate-specific Antigen Levels in Patients with Recurrent Prostate Cancer after Radical Prostatectomy. Clin. Cancer Res. 6: 3845-3849 [Abstract] [Full Text]  
• van Zandwijk, N., Dalesio, O., Pastorino, U., de Vries, N., van Tinteren, H. (2000). EUROSCAN, a Randomized Trial of Vitamin A and N-Acetylcysteine in Patients With Head and Neck Cancer or Lung Cancer. JNCI J Natl Cancer Inst 92: 977-986 [Abstract] [Full Text]  
• Zeng, Q., Smith, D. C., Suscovich, T. J., Gooding, W. E., Trump, D. L., Grandis, J. R. (2000). Determination of Intermediate Biomarker Expression Levels by Quantitative Reverse Transcription-Polymerase Chain Reaction in Oral Mucosa of Cancer Patients Treated with Liarozole. Clin. Cancer Res. 6: 2245-2251 [Abstract] [Full Text]  
• Lee, J. J., Hong, W. K., Hittelman, W. N., Mao, L., Lotan, R., Shin, D. M., Benner, S. E., Xu, X.-C., Lee, J. S., Papadimitrakopoulou, V. M., Geyer, C., Perez, C., Martin, J. W., El-Naggar, A. K., Lippman, Scott. M. (2000). Predicting Cancer Development in Oral Leukoplakia: Ten Years of Translational Research. Clin. Cancer Res. 6: 1702-1710 [Abstract] [Full Text]  
• Vokes, E. E., Kies, M. S., Haraf, D. J., Stenson, K., List, M., Humerickhouse, R., Dolan, M. E., Pelzer, H., Sulzen, L., Witt, M. E., Hsieh, Y.-C., Mittal, B. B., Weichselbaum, R. R. (2000). Concomitant Chemoradiotherapy as Primary Therapy for Locoregionally Advanced Head and Neck Cancer. JCO 18: 1652-1661 [Abstract] [Full Text]  
• Lippman, S. M., Lotan, R. (2000). Advances in the Development of Retinoids as Chemopreventive Agents. J. Nutr. 130: 479-479 [Abstract] [Full Text]  
• Shin, D. M., Mao, L., Papadimitrakopoulou, V. M., Clayman, G., El-Naggar, A., Shin, H. J. C., Lee, J. J., Lee, J. S., Gillenwater, A., Myers, J., Lippman, S. M., Hittelman, W. N., Hong, W. K. (2000). Biochemopreventive Therapy for Patients With Premalignant Lesions of the Head and Neck and p53 Gene Expression. JNCI J Natl Cancer Inst 92: 69-73 [Full Text]  
• Lotan, Y., Xu, X. C., Shalev, M., Lotan, R., Williams, R., Wheeler, T. M., Thompson, T. C., Kadmon, D. (2000). Differential Expression of Nuclear Retinoid Receptors in Normal and Malignant Prostates. JCO 18: 116-116 [Abstract] [Full Text]  
• Garewal, H. S., Katz, R. V., Meyskens, F., Pitcock, J., Morse, D., Friedman, S., Peng, Y., Pendrys, D. G., Mayne, S., Alberts, D., Kiersch, T., Graver, E. (1999). {beta}-Carotene Produces Sustained Remissions in Patients With Oral Leukoplakia: Results of a Multicenter Prospective Trial. Arch Otolaryngol Head Neck Surg 125: 1305-1310 [Abstract] [Full Text]  
• Mulshine, J. L. (1999). Reducing Lung Cancer Risk* : Early Detection. Chest 116 : 493S-496S [Abstract] [Full Text]  
• Lippman, S. M., Brown, P. H. (1999). Tamoxifen Prevention of Breast Cancer: an Instance of the Fingerpost. JNCI J Natl Cancer Inst 91: 1809-1819 [Full Text]  
• McCaskill-Stevens, W., Hawk, E. T., Flynn, P. J., Lippman, S. M. (1999). National Cancer Institute-Supported Cancer Chemoprevention Research: Coming of Age. JCO 17: 53-62 [Full Text]  
• (1999). Prevention of Cancer in the Next Millennium: Report of the Chemoprevention Working Group to the American Association for Cancer Research. Cancer Res. 59: 4743-4758 [Full Text]  
• Papadimitrakopoulou, V. A., Clayman, G. L., Shin, D. M., Myers, J. N., Gillenwater, A. M., Goepfert, H., El-Naggar, A. K., Lewin, J. S., Lippman, S. M., Hong, W. K. (1999). Biochemoprevention for Dysplastic Lesions of the Upper Aerodigestive Tract. Arch Otolaryngol Head Neck Surg 125: 1083-1089 [Abstract] [Full Text]  
• Xu, X.-C., Liu, X., Tahara, E., Lippman, S. M., Lotan, R. (1999). Expression and Up-Regulation of Retinoic Acid Receptor-{beta} Is Associated with Retinoid Sensitivity and Colony Formation in Esophageal Cancer Cell Lines. Cancer Res. 59: 2477-2483 [Abstract] [Full Text]  
• Seewaldt, V. L., Dietze, E. C., Johnson, B. S., Collins, S. J., Parker, M. B. (1999). Retinoic Acid-mediated G1-S-Phase Arrest of Normal Human Mammary Epithelial Cells Is Independent of the Level of p53 Protein Expression. Cell Growth Differ. 10: 49-59 [Abstract] [Full Text]  
• Olmedilla, B., Granado, F., Blanco, I., Rojas-Hidalgo, E. (1996). Evaluation of Retinol, {alpha}-Tocopherol, and Carotenoids in Serum of Men With Cancer of the Larynx Before and After Commercial Enteral Formula Feeding. JPEN J Parenter Enteral Nutr 20: 145-149 [Abstract]  
• Trump, B. F. (1995). Mechanisms of Toxicity and Carcinogenesis. Toxicol Pathol 23: 775-827  
• Chairman, T.A., Downer, M.C. (1995). Early Diagnosis and Prevention of Oral Cancer and Precancer: Report of Symposium III. ADR 9: 134-137 [Abstract]  
• Lotan, R., Xu, X.-C., Lippman, S. M., Ro, J. Y., Lee, J. S., Lee, J. J., Hong, W. K. (1995). Suppression of Retinoic Acid Receptor-{beta} in Premalignant Oral Lesions and Its Up-Regulation by Isotretinoin. NEJM 332: 1405-1411 [Abstract] [Full Text]  
• Johns, M. E., Richtsmeier, W. J. (1994). Otolaryngology--Head and Neck Surgery. JAMA 271: 1698-1700 [Abstract]  
• Vokes, E. E., Weichselbaum, R. R., Lippman, S. M., Hong, W. K. (1993). Head and Neck Cancer. NEJM 328: 184-194 [Full Text]  
• Richtsmeier, W. J. (1993). Biologic Modifiers and Chemoprevention of Cancer of the Oral Cavity. NEJM 328: 58-59 [Full Text]