A Phase II Multi-institutional Trial of Chemoradiation Using Weekly Docetaxel and Erythropoietin for High-Risk Postoperative Head and Neck Cancer Patients

Willey, Christopher D.; Murphy, Barbara A.; Netterville, James L.; Burkey, Brian B.; Shyr, Yu; Shakhtour, Bashar; Kish, Bonnie; Raben, David; Chen, Changhu; Song, John I.; Kane, Madeleine A.; Cmelak, Anthony J.

doi:10.1016/j.ijrobp.2006.11.033

« Previous Next »International Journal of Radiation Oncology * Biology * Physics
Volume 67, Issue 5 , Pages 1323-1331, 1 April 2007

A Phase II Multi-institutional Trial of Chemoradiation Using Weekly Docetaxel and Erythropoietin for High-Risk Postoperative Head and Neck Cancer Patients

The results of this study were previously presented at the 2004 American Society of Clinical Oncology meeting.

Christopher D. Willey, M.D., Ph.D.
- Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
Barbara A. Murphy, M.D.
- Department of Medical Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
James L. Netterville, M.D.
- Department of Otolaryngology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
Brian B. Burkey, M.D.
- Department of Otolaryngology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
Yu Shyr, Ph.D.
- Department of Head and Neck Surgery, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
Bashar Shakhtour, B.S.
- Department of Head and Neck Surgery, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
Bonnie Kish, R.N.
- Department of Biostatistics, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
David Raben, M.D.
- Department of Clinical Trials Office, Vanderbilt University Medical Center, Nashville, Tennessee
Changhu Chen, M.D.
- Department of Radiation Oncology, University of Colorado Health Sciences Center, Denver, Colorado
John I. Song, M.D.
- Department of Otolaryngology, University of Colorado Health Sciences Center, Denver, Colorado
Madeleine A. Kane, M.D., Ph.D.
- Department of Medical Oncology, University of Colorado Health Sciences Center, Denver, Colorado
Anthony J. Cmelak, M.D.
- Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
- Reprint requests to: Anthony J. Cmelak, M.D., Radiation Oncology, Vanderbilt-Ingram Cancer Center, B-902, The Vanderbilt Clinic, Nashville, TN 37232-5671. Tel: (615) 343-9462; Fax: (615) 343-0161

Received 11 September 2006; received in revised form 14 November 2006; accepted 17 November 2006. published online 07 February 2007.

Purpose: To determine efficacy and toxicities of postoperative concurrent chemoradiation using docetaxel in high-risk head and neck cancer.

Methods and Materials: High-risk patients were enrolled 2–8 weeks after surgery. Treatment included 60 Gy for 6 weeks with weekly docetaxel 25 mg/m² and erythropoietin alpha 40,000 U for hemoglobin ≤12 g/dL. Primary endpoints included locoregional control (LC), disease-free survival (DFS), and patterns of failure (POF). Secondary endpoints were toxicity and quality of life.

Results: Eighteen patients were enrolled (14 male, 4 female), aged 24–70 years (median, 55 years). Primary site included oropharynx = 7, oral cavity = 8, hypopharynx = 1, and larynx = 2. Pathologic American Joint Committee on Cancer Stage was III = 3 patients, IV = 15 patients. High-risk eligibility included ≥2 positive lymph nodes = 13, extracapsular extension = 10, positive margins = 8 (11 patients with two or more risk factors). Docetaxel was reduced to 20 mg/m²/week after 5 patients had prolonged Grade 3 or higher mucositis. Overall, number of doses delivered was 2 of 6 = 1, 3 of 6 = 2, 4 of 6 = 2, 5 of 6 = 4, 6 of 6 = 9 patients. With median follow-up of 30 months (range, 5–66), 10 (56%) patients are alive and have no evidence of disease (NED); POF: three local recurrences (two with distant) and 1 distant only. One-year survival was 76%, median PFS and DFS had not been reached. Three-year LC was 82%. No Grade 3 or higher late toxicities were observed, although a few cases of prolonged mucositis and taste loss (>3 months) were seen, particularly at 25 mg/m²/week.

Conclusion: Postoperative radiation therapy with weekly docetaxel 20 or 25 mg/m²/week for high-risk postoperative head and neck cancer caused intolerable mucosal toxicity, prompting early study termination. Further studies should consider 15 mg/m². Actuarial 3-year LC is 82%, similar to cisplatin-based chemoradiation regimens. Distant metastasis remains an important issue requiring additional systemic interventions.

Keywords: Chemoradiation, Docetaxel, Postoperative, Head and neck cancer, Clinical trial