Originally published as JCO Early Release 10.1200/JCO.2003.03.544 on November 3 2003

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rudin, C. M. Articles by Vokes, E. E. Search for Related Content PubMed PubMed Citation Articles by Rudin, C. M. Articles by Vokes, E. E. Social Bookmarking                            What's this?

An Attenuated Adenovirus, ONYX-015, As Mouthwash Therapy for Premalignant Oral Dysplasia

Charles M. Rudin, Ezra E.W. Cohen, Vassiliki A. Papadimitrakopoulou, Sol Silverman, Jr, Wendy Recant, Adel K. El-Naggar, Kirsten Stenson, Scott M. Lippman, Waun Ki Hong, Everett E. Vokes

From the University of Chicago, Chicago, IL; M.D. Anderson Cancer Center, Houston, TX; and the University of California San Francisco, San Francisco, CA.

Address reprint requests to Charles M. Rudin, MD, PhD, University of Chicago Medical Center, 5841 S Maryland Ave, MC2115, Chicago, IL 60637; e-mail: crudin{at}medicine.bsd.uchicago.edu.

Purpose: Dysplastic lesions of the oral epithelium are known precursors of oral cancer. A significant proportion of oral dysplastic lesions have functional defects in p53 response pathways. The ONYX-015 adenovirus is selectively cytotoxic to cells carrying defects in p53-dependent signaling pathways. The current study sought to establish the feasibility and activity of ONYX-015 administered topically as a mouthwash to patients with clinically apparent and histologically dysplastic lesions of the oral mucosa.

Patients and Methods: A total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX-015 was administered on three different schedules to consecutive cohorts. Biopsies of the involved mucosa were performed to evaluate histologic response and changes in expression of putative markers of malignant potential, including p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral titers.

Results: Histologic resolution of dysplasia was seen in seven (37%) of 19 patients, and the grade of dysplasia improved in one additional patient. The majority of responses were transient. No toxicity greater than grade 2 (febrile episode in one patient) was observed. Only one of seven patients demonstrated an increase in circulating antiadenoviral antibody titer while on therapy. Although responding and resistant lesions had similar mean p53 staining at baseline, histologic response correlated with a decrease in p53 positivity over time. Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication was confirmed in two of three lesions examined.

Conclusion: This novel approach to cancer prevention is tolerable, feasible, and has demonstrable activity.

Supported by the Francis Lederer Foundation, grant no. NIH 5 P50 DECA11921-04 from the National Institutes of Health, and ONYX Pharmaceuticals.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. Szabo Assessing Efficacy in Early-Phase Cancer Prevention Trials: The Case of Oral Premalignancy Cancer Prevention Research, October 1, 2008; 1(5): 312 - 315. [Full Text] [PDF]

				S. R. Mallery, J. C. Zwick, P. Pei, M. Tong, P. E. Larsen, B. S. Shumway, B. Lu, H. W. Fields, R. J. Mumper, and G. D. Stoner Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions Cancer Res., June 15, 2008; 68(12): 4945 - 4957. [Abstract] [Full Text] [PDF]

				B. S. Shumway, L. A. Kresty, P. E. Larsen, J. C. Zwick, B. Lu, H. W. Fields, R. J. Mumper, G. D. Stoner, and S. R. Mallery Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions Clin. Cancer Res., April 15, 2008; 14(8): 2421 - 2430. [Abstract] [Full Text] [PDF]

				F. R. Khuri and D. M. Shin Head and Neck Cancer Chemoprevention Gets a Shot in the Arm J. Clin. Oncol., January 20, 2008; 26(3): 345 - 347. [Full Text] [PDF]

				S. Choi and J.N. Myers Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy Journal of Dental Research, January 1, 2008; 87(1): 14 - 32. [Abstract] [Full Text] [PDF]

				K. Gaballah, A. Hills, D. Curiel, G. Hallden, P. Harrison, and M. Partridge Lysis of Dysplastic but not Normal Oral Keratinocytes and Tissue-Engineered Epithelia with Conditionally Replicating Adenoviruses Cancer Res., August 1, 2007; 67(15): 7284 - 7294. [Abstract] [Full Text] [PDF]

				D. Cross and J. K. Burmester Gene therapy for cancer treatment: past, present and future. Clin. Med. Res., September 1, 2006; 4(3): 218 - 227. [Abstract] [Full Text] [PDF]

				M.S. Pinsky, W. Song, Z. Dong, K. Warner, B. Zeitlin, E. Karl, D.E. Hall, and J.E. Nor Activation of iCaspase-9 in Neovessels Inhibits Oral Tumor Progression Journal of Dental Research, May 1, 2006; 85(5): 436 - 441. [Abstract] [Full Text] [PDF]

				F. R. Khuri, J. J. Lee, S. M. Lippman, E. S. Kim, J. S. Cooper, S. E. Benner, R. Winn, T. F. Pajak, B. Williams, G. Shenouda, 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, April 5, 2006; 98(7): 441 - 450. [Abstract] [Full Text] [PDF]

				B. J.M. Braakhuis, R. H. Brakenhoff, and C. R. Leemans Second Field Tumors: A New Opportunity for Cancer Prevention? Oncologist, August 1, 2005; 10(7): 493 - 500. [Abstract] [Full Text] [PDF]

				S. M. Lippman and B. Levin Cancer Prevention: Strong Science and Real Medicine J. Clin. Oncol., January 10, 2005; 23(2): 249 - 253. [Full Text] [PDF]

				S. M. Lippman, J. Sudbo, and W. K. Hong Oral Cancer Prevention and the Evolution of Molecular-Targeted Drug Development J. Clin. Oncol., January 10, 2005; 23(2): 346 - 356. [Abstract] [Full Text] [PDF]

				R. L. Chu, D. E. Post, F. R. Khuri, and E. G. Van Meir Use of Replicating Oncolytic Adenoviruses in Combination Therapy for Cancer Clin. Cancer Res., August 15, 2004; 10(16): 5299 - 5312. [Abstract] [Full Text] [PDF]

				J. C. Rhee, F. R. Khuri, and D. M. Shin Advances in Chemoprevention of Head and Neck Cancer Oncologist, June 1, 2004; 9(3): 302 - 311. [Abstract] [Full Text] [PDF]

				I. Ganly and B. Singh Topical ONYX-015 in the Treatment of Premalignant Oral Dysplasia: Another Role for the Cold Virus? J. Clin. Oncol., December 15, 2003; 21(24): 4476 - 4478. [Full Text] [PDF]