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Egloff AM , Lee JW , Langer CJ , Quon H , Vaezi A , Grandis JR , Seethala RR , Wang L , Shin DM , Argiris A , Yang D , Mehra R , Ridge JA , Patel UA , Burtness BA , Forastiere AA
Phase II Study of Cetuximab in Combination with Cisplatin and Radiation in Unresectable, Locally Advanced Head and Neck Squamous Cell Carcinoma: Eastern Cooperative Oncology Group Trial E3303
Clin Cancer Res. 2014 Oct 1;20(19) :5041-51
PMID: 25107914   
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PURPOSE: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. EXPERIMENTAL DESIGN: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m(2)) followed by 250 mg/m(2)/week and cisplatin 75 mg/m(2) q 3 weeks x3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. RESULTS: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%-61%]. Two-year overall survival (OS) was 66% (95% CI, 53%-77%); median OS was not reached. Response rate was 66.7%. Most common grade >/=3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV(+) patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). CONCLUSIONS: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV(+) tumors. Clin Cancer Res; 20(19); 5041-51. (c)2014 AACR.
Egloff, Ann Marie Lee, Ju-Whei Langer, Corey J Quon, Harry Vaezi, Alec Grandis, Jennifer R Seethala, Raja R Wang, Lin Shin, Dong M Argiris, Athanassios Yang, Donghua Mehra, Ranee Ridge, John Andrew Patel, Urjeet A Burtness, Barbara A Forastiere, Arlene A K07 CA137140/CA/NCI NIH HHS/United States R01 DE023685/DE/NIDCR NIH HHS/United States Journal Article United States Clin Cancer Res. 2014 Oct 1;20(19):5041-51. doi: 10.1158/1078-0432.CCR-14-0051. Epub 2014 Aug 8.