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Originally published as JCO Early Release 10.1200/JCO.2007.12.7597 on May 12 2008 © 2008 American Society of Clinical Oncology. Chemoselection As a Strategy for Organ Preservation in Advanced Oropharynx Cancer: Response and Survival Positively Associated With HPV16 Copy Number
From the Department of Internal Medicine, Division of Hematology-Oncology, Department of Otolaryngology–Head and Neck Surgery, Comprehensive Cancer Center, Department of Periodontics and Oral Medicine, Department of Pathology, Department of Biostatistics, Department of Radiation Oncology; Department of Pediatrics, and Department of Pharmacology, University of Michigan, Ann Arbor, MI Corresponding author: Francis P. Worden, MD, 1500 E Medical Center Dr, C361 MIB 0848, Ann Arbor, MI, 48109-0848; e-mail: fworden{at}umich.edu Purpose To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome. Patients and Methods Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m2) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m2/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m2 or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV. Results Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008). Conclusion Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed. Supported in part by Grants No. R01 DE13346 and P30 DC 05188 from the National Institutes of Health (NIH) NIDCR; Head and Neck Cancer SPORE Grant No. P50 CA97248; Cancer Center Support Grant No. P30 CA46592; and Grants from the state of Michigan. Both F.P.W. and B.K. contributed equally to this work. Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, 2002, Orlando, FL; 6th International Conference on Head and Neck Cancer, August 9, 2004, Washington, DC; 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; American Association for Cancer Research Meeting, April 4, 2006, Washington, DC; and Multidisciplinary Head and Neck Cancer Symposium, January 18-20, 2007, Rancho Mirage, CA. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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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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