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Annals of Oncology Advance Access originally published online on June 6, 2008
Annals of Oncology 2008 19(10):1787-1794; doi:10.1093/annonc/mdn364
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

head and neck cancer

Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels

J. K. Salama1,3, K. M. Stenson3,5, E. O. Kistner4, B. B. Mittal6, A. Argiris9, M. E. Witt1, F. Rosen8, B. E. Brockstein7, E. E. W. Cohen2,3, D. J. Haraf1,3 and E. E. Vokes1,2,3,*

1 Department of Radiation and Cellular Oncology
2 Section of Hematology/Oncology, Department of Medicine
3 The Cancer Research Center
4 Biostatistics Laboratory, Department of Health Studies
5 Section of Otolaryngology Head and Neck Surgery, Department of Surgery, University of Chicago, Chicago, IL
6 Feinberg School of Medicine, Northwestern University, Chicago, IL
7 Feinberg School of Medicine, Evanston Northwestern Healthcare, Northwestern University, Evanston, IL
8 John H. Stroger, Jr. Hospital of Cook County, Chicago, IL
9 University of Pittsburgh Medical Center, Pittsburgh, PA

* Correspondence to: Dr E. E. Vokes, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637, USA. Tel: +1-773-702-3002; Fax: +1-773-702-3002; E-mail: evokes{at}medicine.bsd.uchicago.edu

Background: We hypothesized induction chemotherapy (IndCT) would improve distant control (DC) without compromising locoregional control (LRC) for locoregionally advanced head and neck cancer patients. Additionally, we systematically lowered radiotherapy (RT) doses attempting to maintain LRC while decreasing toxicity.

Patients and methods: Stages III–IV (M0) locoregionally advanced head and neck cancer patients received carboplatin/paclitaxel (Taxol) IndCT followed by four or five cycles consisting of 5 days of paclitaxel, fluorouracil, hydroxyurea, and BID RT followed by a nine day break. RT dose to gross disease (high risk), intermediate, and low-risk volumes were reduced from cohort A (n = 68): 75, 60, and 45 Gy; to cohort B (n = 64): 75, 54, and 39 Gy; then cohort C (n = 90): 72, 51, and 36 Gy.

Results: A total of 222 patients accrued from November 1998 to September 2002. Median follow-up is 56 months. In all, 93/96/76% achieved a complete response to concurrent chemoradiotherapy (CRT) in cohort A/B/C. Three- and 5-year overall survivals (OSs) are 68% and 62%, respectively. Five-year LRC and DC are 91% and 87%, respectively. Response to IndCT predicted for OS, LRC, and time to progression (TTP). Cohort C patients had similar OS (P = 0.95), LRC, and DC, but worse (TTP) (P = 0.027).

Conclusions: IndCT before CRT reduces distant progression while maintaining high LRC. The cohort B schedule provides the best therapeutic ratio. A randomized trial investigating IndCT before CRT has been initiated.

Key words: chemoradiotherapy, induction chemotherapy, locoregionally advanced head and neck cancer

Received for publication February 22, 2008. Revision received April 21, 2008. Accepted for publication April 22, 2008.


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