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 357:1695-1704 October 25, 2007 Number 17 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.

Methods We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival.

Results A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group.

Conclusions As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov] .)

Source Information

From Universitair Ziekenhuis Antwerpen, Edegem, Belgium (J.B.V.); the National Institute of Oncology, Budapest, Hungary (E.R.); Universitair Medisch Centrum Nijmegen, Nijmegen, the Netherlands (C.H.); EORTC Data Center, Brussels (T.G., I.D.); Institut Catala d'Oncologia, Barcelona (R.M.); Centre Oscar Lambret, Lille, France (M.D., J.-L.L.); Charing Cross Hospital, London (J.S.S.); the Institute of Oncology and Radiology, Belgrade, Serbia (S.J.); University Hospital Motol, Prague, Czech Republic (J. Betka); Caritasklinik St. Theresia, Saarbrucken, Germany (J.H.P.); Ziekenhuis Netwerk Antwerpen Middelheim, Antwerp, Belgium (D.W.); Institut Jules Bordet, Brussels (A.A.); Centre Régional de Lutte contre le Cancer Val d'Aurelle, Montpellier, France (D.C.); Kaiser Franz Josef Spital, Vienna (H.R.K.); Sanofi-Aventis Global Oncology, Paris (A.R.); and Clinique de Genolier, Genolier, Switzerland (J. Bernier).

Address reprint requests to Dr. Vermorken at the Department of Medical Oncology, Universitair Ziekenhuis Antwerpen, Wilrijkstraat 10, 2650 Edegem, Belgium, or at jan.b.vermorken{at}uza.be.

Full Text of this Article

Related Letters:

Chemotherapy in Unresectable Head and Neck Cancer
Bölke E., Peiper M., Gripp S., Vermorken J. B.
Extract | Full Text | PDF  
N Engl J Med 2008; 358:1075, Mar 6, 2008. Correspondence

This article has been cited by other articles:

• Haddad, R. I., Tishler, R. B., Norris, C., Goguen, L., Balboni, T. A., Costello, R., Wirth, L., Lorch, J., Andreozzi, B., Annino, D., Posner, M. R. (2009). Phase I Study of C-TPF in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. JCO 27: 4448-4453 [Abstract] [Full Text]  
• Haddad, R. I., Posner, M. R. (2009). Induction Chemotherapy in Head and Neck Cancer. JCO 27: e52-e53 [Full Text]  
• Beitler, J. J., Cooper, J. S. (2009). Reply to R.I. Haddad et al. JCO 27: e54-e54 [Full Text]  
• Koh, Y., Kim, T. M., Jeon, Y. K., Kwon, T.-K., Hah, J. H., Lee, S.-H., Kim, D.-W., Wu, H.-G., Rhee, C.-S., Sung, M.-W., Kim, C. W., Kim, K. H., Heo, D. S. (2009). Class III {beta}-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma. Ann Oncol 20: 1414-1419 [Abstract] [Full Text]  
• THOMAS, C. Y., READ, P., PETRONI, G., REIBEL, J., LEVINE, P. A. (2009). Phase I Study of Capecitabine, Carboplatin and Intensity-modulated Radiation Therapy for Head and Neck Cancer. Anticancer Res 29: 2869-2873 [Abstract] [Full Text]  
• Yeh, E. T.H., Bickford, C. L. (2009). Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management.. J Am Coll Cardiol 53: 2231-2247 [Abstract] [Full Text]  
• Posner, M. R., Norris, C. M., Wirth, L. J., Shin, D. M., Cullen, K. J., Winquist, E. W., Blajman, C. R., Mickiewicz, E. A., Frenette, G. P., Plinar, L. F., Cohen, R. B., Steinbrenner, L. M., Freue, J. M., Gorbunova, V. A., Tjulandin, S. A., Raez, L. E., Adkins, D. R., Tishler, R. B., Roessner, M. R., Haddad, R. I., for the TAX 324 Study Group, (2009). Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation. Ann Oncol 20: 921-927 [Abstract] [Full Text]  
• Licitra, L., Felip, E., On behalf of the ESMO Guidelines Working Group, (2009). Squamous cell carcinoma of the head and neck: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol 20: iv121-iv122 [Full Text]  
• Holsinger, F. C., Kies, M. S., Diaz, E. M. Jr, Gillenwater, A. M., Lewin, J. S., Ginsberg, L. E., Glisson, B. S., Garden, A. S., Ark, N., Lin, H. Y., Lee, J. J., El-Naggar, A. K., Ki Hong, W., Shin, D. M., Khuri, F. R. (2009). Durable Long-Term Remission With Chemotherapy Alone for Stage II to IV Laryngeal Cancer. JCO 27: 1976-1982 [Abstract] [Full Text]  
• Pointreau, Y., Garaud, P., Chapet, S., Sire, C., Tuchais, C., Tortochaux, J., Faivre, S., Guerrif, S., Alfonsi, M., Calais, G. (2009). Randomized Trial of Induction Chemotherapy With Cisplatin and 5-Fluorouracil With or Without Docetaxel for Larynx Preservation. JNCI J Natl Cancer Inst 101: 498-506 [Abstract] [Full Text]  
• Ashimori, N., Zeitlin, B. D., Zhang, Z., Warner, K., Turkienicz, I. M., Spalding, A. C., Teknos, T. N., Wang, S., Nor, J. E. (2009). TW-37, a small-molecule inhibitor of Bcl-2, mediates S-phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Molecular Cancer Therapeutics 8: 893-903 [Abstract] [Full Text]  
• Diaz, R., Blakey, M. D., Murphy, P. B., Cryar, A. K., Cmelak, A. J. (2009). Thyroid Storm After Intensity-Modulated Radiation Therapy: A Case Report and Discussion. The Oncologist 14: 233-239 [Abstract] [Full Text]  
• Lefebvre, J. L., Rolland, F., Tesselaar, M., Bardet, E., Leemans, C. R., Geoffrois, L., Hupperets, P., Barzan, L., de Raucourt, D., Chevalier, D., Licitra, L., Lunghi, F., Stupp, R., Lacombe, D., Bogaerts, J., Horiot, J. C., Bernier, J., Vermorken, J. B., for the EORTC Head and Neck Cancer Cooperative Gro, (2009). Phase 3 Randomized Trial on Larynx Preservation Comparing Sequential vs Alternating Chemotherapy and Radiotherapy. JNCI J Natl Cancer Inst 101: 142-152 [Abstract] [Full Text]  
• Forastiere, A. A., Trotti, A. M. (2009). Searching for Less Toxic Larynx Preservation: A Need for Common Definitions and Metrics. JNCI J Natl Cancer Inst 101: 129-131 [Full Text]  
• Hui, E. P., Ma, B. B., Leung, S. F., King, A. D., Mo, F., Kam, M. K., Yu, B. K., Chiu, S. K., Kwan, W. H., Ho, R., Chan, I., Ahuja, A. T., Zee, B. C., Chan, A. T. (2009). Randomized Phase II Trial of Concurrent Cisplatin-Radiotherapy With or Without Neoadjuvant Docetaxel and Cisplatin in Advanced Nasopharyngeal Carcinoma. JCO 27: 242-249 [Abstract] [Full Text]  
• Beitler, J. J., Cooper, J. S. (2009). Seduction by Induction?. JCO 27: 9-10 [Full Text]  
• Haddad, R. I., Shin, D. M. (2008). Recent Advances in Head and Neck Cancer. NEJM 359: 1143-1154 [Full Text]  
• Glynne-Jones, R., Mawdsley, S. (2008). Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy?. JCO 26: 3669-3671 [Full Text]  
• Ang, K. K. (2008). Multidisciplinary Management of Locally Advanced SCCHN: Optimizing Treatment Outcomes. The Oncologist 13: 899-910 [Abstract] [Full Text]  
• Singh, B., Pfister, D. G. (2008). Individualized Treatment Selection in Patients With Head and Neck Cancer: Do Molecular Markers Meet the Challenge?. JCO 26: 3114-3116 [Full Text]  
• Adelstein, D. J. (2008). Redefining the Role of Induction Chemotherapy in Head and Neck Cancer. JCO 26: 3117-3119 [Full Text]  
• Yoo, G. H., Subramanian, G., Piechocki, M. P., Ensley, J. F., Kucuk, O., Tulunay, O. E., Lonardo, F., Kim, H., Won, J., Stevens, T., Lin, H.-S. (2008). Effect of Docetaxel on the Surgical Tumor Microenvironment of Head and Neck Cancer in Murine Models. Arch Otolaryngol Head Neck Surg 134: 735-742 [Abstract] [Full Text]  
• Marur, S., Forastiere, A. A. (2008). Head and Neck Cancer: Changing Epidemiology, Diagnosis, and Treatment. Mayo Clin Proc. 83: 489-501 [Abstract] [Full Text]  
• Bolke, E., Peiper, M., Gripp, S., Vermorken, J. B. (2008). Chemotherapy in Unresectable Head and Neck Cancer. NEJM 358: 1075-1075 [Full Text]  
• Forastiere, A., Weber, R., Ang, K., Trotti, A. III, Pajak, T. F., Ridge, J. A., Saghir, F., Feldman, L. E., Nutting, C. M., Bhide, S. A., Harrington, K. J., Posner, M. R., Haddad, R. I., Tishler, R. B. (2008). Treatment of head and neck cancer.. NEJM 358: 1076-1076 [Full Text]  
• Kies, M. S., Blumenschein, G. R. Jr., Rosenthal, D. I. (2008). Sequential Chemoradiation for Squamous Cell Carcinoma of the Head and Neck. Am Soc Clin Oncol Ed Book 2008: 235-238 [Abstract] [Full Text]  
• Posner, M. R., Hershock, D. M., Blajman, C. R., Mickiewicz, E., Winquist, E., Gorbounova, V., Tjulandin, S., Shin, D. M., Cullen, K., Ervin, T. J., Murphy, B. A., Raez, L. E., Cohen, R. B., Spaulding, M., Tishler, R. B., Roth, B., Viroglio, R. d. C., Venkatesan, V., Romanov, I., Agarwala, S., Harter, K. W., Dugan, M., Cmelak, A., Markoe, A. M., Read, P. W., Steinbrenner, L., Colevas, A. D., Norris, C. M. Jr., Haddad, R. I., the TAX 324 Study Group, (2007). Cisplatin and Fluorouracil Alone or with Docetaxel in Head and Neck Cancer. NEJM 357: 1705-1715 [Abstract] [Full Text]