Single Arm, Phase II Study of Cisplatin, Docetaxel, and Erlotinib in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinomas
William N William Jr, Anne S Tsao, Lei Feng, Lawrence E Ginsberg, J Jack Lee, Merrill S Kies, Bonnie S Glisson, Edward S Kim, William N William Jr, Anne S Tsao, Lei Feng, Lawrence E Ginsberg, J Jack Lee, Merrill S Kies, Bonnie S Glisson, Edward S Kim
Abstract
Lessons learned: The combination of cisplatin, docetaxel, and erlotinib as frontline treatment for recurrent and/or metastatic head and neck squamous cell carcinomas led to a response rate of 62%.This result exceeded the prespecified target response rate of 50% and represented an improvement compared with historical controls.This regimen warrants further investigation.
Background: The epidermal growth factor receptor (EGFR) plays a key role in the carcinogenesis of head and neck squamous cell carcinomas (HNSCC). We conducted this clinical study to test the hypothesis that the addition of erlotinib to first-line cisplatin and docetaxel for patients with recurrent and/or metastatic HNSCC would yield a response rate of at least 50%, representing an improvement from historical controls.
Methods: Patients with recurrent and/or metastatic HNSCC, with at least one measurable lesion, no prior chemotherapy for recurrent and/or metastatic disease, prior combined modality therapy completed >6 months before enrollment, and performance status ≤2 were treated with cisplatin, docetaxel, and erlotinib for up to six cycles, followed by maintenance erlotinib until disease progression. The primary endpoint was response rate.
Results: Fifty patients were enrolled (42 male, 12 never smokers, 19 with oropharynx cancer). The median number of cycles was five; 31 patients initiated maintenance erlotinib; 14 patients required erlotinib dose reductions. The objective response rate was 62%, and the median progression-free and overall survival were 6.1 and 11.0 months, respectively. Toxicity profiles were consistent with the known side effects of the study drugs.
Conclusion: The study met its primary endpoint and improved response rates compared with historical controls. The findings support further evaluation of the regimen for recurrent and/or metastatic HNSCCs.
Trial registration: ClinicalTrials.gov NCT00076310.
Conflict of interest statement
Disclosures of potential conflicts of interest may be found at the end of this article.
©AlphaMed Press; the data published online to support this summary is the property of the authors.
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References
- Glisson BS, Murphy BA, Frenette G et al. Phase II trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck. J Clin Oncol 2002;20:1593–1599.
- Soulieres D, Senzer NN, Vokes EE et al. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol 2004;22:77–85.
- Cohen EE, Rosen F, Stadler WM et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 2003;21:1980–1987.
- Cohen EE, Kane MA, List MA et al. Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res 2005;11:8418–8424.
- Stewart JS, Cohen EE, Licitra L et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol 2009;27:1864–1871.
- Machiels JP, Haddad RI, Fayette J et al. Afatinib versus methotrexate as second‐line treatment in patients with recurrent or metastatic squamous‐cell carcinoma of the head and neck progressing on or after platinum‐based therapy (LUX‐Head & Neck 1): An open‐label, randomised phase 3 trial. Lancet Oncol 2015;16:583–594.
- William WN Jr, Weber RS, Lee JJ et al. Randomized trial of a short course of erlotinib 150 to 300 mg daily prior to surgery for squamous cell carcinomas of the head and neck (SCCHN) in current, former, and never smokers: Objective responses and clinical outcomes J Clin Oncol 2011;29(suppl 15):5520A.
- Thomas F, Rochaix P, Benlyazid A et al. Pilot study of neoadjuvant treatment with erlotinib in nonmetastatic head and neck squamous cell carcinoma. Clin Cancer Res 2007;13:7086–7092.
- Siu LL, Soulieres D, Chen EX et al. Phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: A Princess Margaret Hospital phase II consortium and National Cancer Institute of Canada clinical trials group study. J Clin Oncol 2007;25:2178–2183.
- Argiris A, Ghebremichael M, Gilbert J et al. Phase III randomized, placebo‐controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: An Eastern Cooperative Oncology Group trial. J Clin Oncol 2013;31:1405–1414.
- Machiels JP, Subramanian S, Ruzsa A et al. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous‐cell carcinoma of the head and neck after failure of platinum‐based chemotherapy: An open‐label, randomised phase 3 trial. Lancet Oncol 2011;12:333–343.
- Vermorken JB, Mesia R, Rivera F et al. Platinum‐based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116–1127.
- Vermorken JB, Stöhlmacher‐Williams J, Davidenko I et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous‐cell carcinoma of the head and neck (SPECTRUM): An open‐label phase 3 randomised trial. Lancet Oncol 2013;14:697–710.
- Vermorken JB, Psyrri A, Mesía R et al. Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: Retrospective analysis of the phase III EXTREME trial. Ann Oncol 2014;25:801–807.
- Licitra L, Mesia R, Rivera F, et al. Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first‐line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol 2011;22:1078–1087.
- William WN, Feng L, Kies MS et al. Randomized, double‐blind, placebo‐controlled, phase II trial of first‐line platinum/docetaxel with or without erlotinib (E) in patients (pts) with recurrent and/or metastatic (R/M) head and neck squamous cell carcinomas (HNSCCs). J Clin Oncol 2017;35(suppl 15):6017A.
Source: PubMed