TY - JOUR
T1 - Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients
T2 - The RTOG Experience
AU - Bar-Ad, Voichita
AU - Zhang, Qiang Ed
AU - Harari, Paul M.
AU - Axelrod, Rita
AU - Rosenthal, David I.
AU - Trotti, Andy
AU - Jones, Christopher U.
AU - Garden, Adam S.
AU - Song, Guobin
AU - Foote, Robert L.
AU - Raben, David
AU - Shenouda, George
AU - Spencer, Sharon A.
AU - Harris, Jonathan
AU - Le, Quynh Thu
N1 - Funding Information:
This project was supported by grants U10CA21661 , U10CA180868 , U10CA180822 , and U10CA37422 from the National Cancer Institute and by Bristol-Myers Squibb .
Funding Information:
Conflict of interest: V.B.-A. reports research funding from Bristol-Myers Squibb and the Radiation Therapy Oncology Group. Q.(E.)Z. reports that an immediate family member is employed by and owns stock in Pfizer. D.I.R. reports stock or other ownership interest in Concordia, a consulting or advisory position with Merck Serono, and research funding from Merck Serono. C.U.J. reports a consulting or advisory position with Lilly and a speakers' bureau with Bristol-Myers Squibb. R.L.F. reports a patent or intellectual property interest from the Mayo Clinic. D.R. reports a consulting or advisory position with Astra Zeneca, Ferring, and Merck. Q.-T.L. reports research funding from Amgen.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Purpose To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.
AB - Purpose To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.
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U2 - 10.1016/j.ijrobp.2016.03.011
DO - 10.1016/j.ijrobp.2016.03.011
M3 - Article
C2 - 27212198
AN - SCOPUS:84975528826
SN - 0360-3016
VL - 95
SP - 1346
EP - 1354
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 5
ER -