Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: A pilot phase II study of a new combined-modality paradigm Journal Article


Authors: Pfister, D. G.; Su, Y. B.; Kraus, D. H.; Wolden, S. L.; Lis, E.; Aliff, T. B.; Zahalsky, A. J.; Lake, S.; Needle, M. N.; Shaha, A. R.; Shah, J. P.; Zelefsky, M. J.
Article Title: Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: A pilot phase II study of a new combined-modality paradigm
Abstract: Purpose: Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy. Patients and Methods: Eligible patients had stage III or IV, M0, squamous cell head and neck cancer. Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m 2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10). Results: Twenty-two patients were enrolled (median age, 57 years; range, 41 to 72 years; median Karnofsky status, 90%; range, 70% to 90%; oropharynx primary tumor, 59% of patients; T4, 36%; N2/3, 77%; stage IV disease, 86%). One patient did not receive study treatment because of an ineligible diagnosis. The severity of expected, acute toxicities was typical of concurrent cisplatin and radiotherapy alone. Grade 3 or 4 cetuximab-related toxicities included acne-like rash (10%) and hypersensitivity (5%). However, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. With a median follow-up of 52 months, the 3-year overall survival rate is 76%, the 3-year progression-free survival rate is 56%, and the 3-year locoregional control rate is 71%. Conclusion: This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. However, preliminary efficacy is encouraging, and further development of this targeted combined-modality paradigm is warranted. © 2006 by American Society of Clinical Oncology.
Keywords: survival; adult; cancer chemotherapy; cancer survival; clinical article; controlled study; human tissue; treatment outcome; treatment response; aged; disease-free survival; middle aged; survival analysis; clinical trial; constipation; cancer localization; squamous cell carcinoma; carcinoma, squamous cell; cisplatin; advanced cancer; cancer growth; side effect; adjuvant therapy; cancer radiotherapy; disease free survival; chemotherapy, adjuvant; radiotherapy, adjuvant; cancer staging; follow up; lymph node metastasis; antineoplastic agent; lymphatic metastasis; neoplasm staging; anorexia; quality of life; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; anemia; kidney disease; leukopenia; nausea; vomiting; antineoplastic combined chemotherapy protocols; dehydration; myalgia; pathology; cetuximab; monoclonal antibody; backache; fever; pneumonia; rash; syncope; acute kidney failure; hypotension; antibodies, monoclonal; disease severity; karnofsky performance status; drug distribution; head and neck cancer; pilot study; head and neck neoplasms; pilot projects; heart infarction; adjuvant chemotherapy; thrombosis; acne; urinary tract infection; bacteremia; drug blood level; embolism; heart arrhythmia; wound infection; bacterial infection; neurologic disease; hallucination; heart atrium fibrillation; metabolic disorder; cytopenia; congestive heart failure; allergic reaction; head and neck tumor; sensorimotor neuropathy; cellulitis; perception deafness; hypersensitivity
Journal Title: Journal of Clinical Oncology
Volume: 24
Issue: 7
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2006-03-01
Start Page: 1072
End Page: 1078
Language: English
DOI: 10.1200/jco.2004.00.1792
PUBMED: 16505426
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 181" - "Export Date: 4 June 2012" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Yungpo Su
    16 Su
  2. Michael J Zelefsky
    615 Zelefsky
  3. Dennis Kraus
    258 Kraus
  4. Ashok R Shaha
    535 Shaha
  5. Eric Lis
    102 Lis
  6. Suzanne L Wolden
    419 Wolden
  7. Timothy Aliff
    7 Aliff
  8. David G Pfister
    247 Pfister
  9. Jatin P Shah
    538 Shah