Randomized Phase II Trial of Concurrent Cisplatin- Radiotherapy With or Without Neoadjuvant Docetaxel and Cisplatin in Advanced Nasopharyngeal Carcinoma Edwin P. Hui, Brigette B. Ma, Sing F. Leung, Ann D. King, Frankie Mo, Michael K. Kam, Brian K. Yu, Samuel K. Chiu, Wing H. Kwan, Rosalie Ho, Iris Chan, Anil T. Ahuja, Benny C. Zee, and Anthony T. Chan From the Department of Clinical Oncol- ogy; Department of Diagnostic Radiol- ogy and Organ Imaging, Prince of Wales Hospital; State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Hong Kong Cancer Institute; Center for Clinical Trials, School of Public Health, The Chinese University of Hong Kong; and Sanofi- aventis Hong Kong, Hong Kong SAR, China. Submitted May 16, 2008; accepted August 18, 2008; published online ahead of print at www.jco.org on December 8, 2008. Supported in part by a research grant from Sanofi-aventis Hong Kong Limited. Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; the 13th European Cancer Conference, October 30-November 3, 2006, Paris, France; and the 43rd Annual Meeting of the American Soci- ety of Clinical Oncology, June 2-5, 2007, Chicago, IL. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: Anthony T. Chan, MD, FRCP, Department of Clini- cal Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China; e-mail: anthonytcchan@cuhk.edu.hk. The Appendix is included in the full-text version of this article, available online at www.jco.org. It is not included in the PDF version (via Adobe® Reader®). © 2008 by American Society of Clinical Oncology 0732-183X/09/2702-242/$20.00 DOI: 10.1200/JCO.2008.18.1545 A B S T R A C T Purpose To compare the toxicities, tumor control, survival, and quality of life of nasopharyngeal cancer (NPC) patients treated with sequential neoadjuvant chemotherapy followed by concurrent cisplatin-radiotherapy (CRT) or CRT alone. Patients and Methods Previously untreated stage III to IVB NPC were randomly assigned to (1) neoadjuvant docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 every 3 weeks for two cycles, followed by cisplatin 40 mg/m 2 /wk concurrent with radiotherapy, or (2) CRT alone. Planned accrual was 30 patients per arm to detect 20% difference of toxicities based on 95% CIs. Results From November 2002 to November 2004, 65 eligible patients were randomly assigned to neoadjuvant chemotherapy followed by CRT (n = 34) or CRT alone (n = 31). There was a high rate of grade 3/4 neutropenia (97%) but not neutropenic fever (12%) during neoadjuvant chemother- apy. No significant differences in rates of acute toxicities were observed between the two arms during CRT. Dose intensities of concurrent cisplatin, late RT toxicities and quality of life scores were comparable in both arms. The 3-year progression-free survival for neoadjuvant versus control arm was 88.2% and 59.5% (hazard ratio = 0.49; 95% CI, 0.20 to 1.19; P = .12). The 3-year overall survival for neoadjuvant versus control arm was 94.1% and 67.7% (hazard ratio = 0.24; 95% CI, 0.078 to 0.73; P = .012). Conclusion Neoadjuvant docetaxel-cisplatin followed by CRT was well tolerated with a manageable toxicity profile that allowed subsequent delivery of full-dose CRT. Preliminary results suggested a positive impact on survival. A phase III study to definitively test this neoadjuvant-concurrent strategy is warranted. J Clin Oncol 27:242-249. © 2008 by American Society of Clinical Oncology INTRODUCTION The current standard treatment for advanced nasopharyngeal cancer (NPC) is concurrent che- moradiotherapy with or without adjuvant chemo- therapy. 1,2 Randomized trials of neoadjuvant chemotherapy followed by RT alone have resulted in encouraging response rates and improvement in disease-free survival, but not overall survival. 3-8 Be- cause the use of chemotherapy in the neoadjuvant setting, or as concurrent therapy to RT, has been consistently shown to improve progression-free survival (PFS) and/or overall survival (OS) in ad- vanced NPC, the development of a sequential schedule of neoadjuvant chemotherapy followed by chemoradiotherapy would seem a logical strategy to maximize the benefit from both approaches. In fact, this “neoadjuvant-concurrent” strategy has been pursued by several groups in uncontrolled phase II studies, with favorable outcome reported. 9-11 The taxanes have demonstrated considerable single-agent activity in head and neck cancers and NPC. 12-16 The combination of paclitaxel and carbo- platin has yielded high response rates in the range of 59% to 75% in metastatic NPC, 17,18 and has demon- strated encouraging activity and safety profile in the neoadjuvant setting of NPC. 11 Docetaxel is associ- ated with less neurotoxicity than paclitaxel and can therefore be more tolerably combined with cispla- tin. Docetaxel and cisplatin in combination is highly JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 27  NUMBER 2  JANUARY 10 2009 242 © 2008 by American Society of Clinical Oncology Downloaded from jco.ascopubs.org on June 21, 2015. For personal use only. No other uses without permission. Copyright © 2009 American Society of Clinical Oncology. 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