DOI: 10.1200/jco.2006.07.6547. 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

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

10.1200/jco.2006.07.6547

Crossref journal-article

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology (233)

Abstract

PurposeTo determine the phase II dose and objective response rate of erlotinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC).Patients and MethodsHNSCC patients with no prior chemotherapy and measurable disease were treated in three escalating-dose cohorts of daily continuous oral (PO) erlotinib and intermittent intravenous (IV) cisplatin given every 21 days. The recommended phase II dose (RPTD) was then evaluated in a two-stage trial with a primary end point of objective response rate.ResultsA total of 51 patients were enrolled. The RPTD was identified as erlotinib 100 mg PO daily and cisplatin 75 mg/m2IV every 21 days. Forty-five patients were treated at the RPTD, of which 44 and 43 were eligible for toxicity and efficacy evaluations, respectively. The intention-to-treat response rate was 21%, with one complete and eight partial responses (95% CI, 10% to 36%), and disease stabilization was achieved in 21 patients (49%; 95% CI, 33% to 65%). Median progression-free survival was 3.3 months (95% CI, 2.7 to 4.8 months) and median overall survival was 7.9 (95% CI, 5.6 to 9.5) months. The combination was well tolerated, with minimal grade 3 or higher toxicity. Subgroup analysis suggested that patients who developed higher grade skin rashes during cycle 1 had better survival outcomes (P = .034).ConclusionThis schedule of erlotinib and cisplatin has a favorable toxicity profile and has antitumor activity in HNSCC comparable to standard combination chemotherapy regimens.

Bibliography

Siu, L. L., Soulieres, D., Chen, E. X., Pond, G. R., Chin, S. F., Francis, P., Harvey, L., Klein, M., Zhang, W., Dancey, J., Eisenhauer, E. A., & Winquist, E. (2007). 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. Journal of Clinical Oncology, 25(16), 2178â2183.

Authors 12

Lillian L. Siu (first)
Denis Soulieres (additional)
Eric X. Chen (additional)
Gregory R. Pond (additional)
Soo F. Chin (additional)
Peggy Francis (additional)
Luc Harvey (additional)
Meri Klein (additional)
Wenjiang Zhang (additional)
Janet Dancey (additional)
Elizabeth A. Eisenhauer (additional)
Eric Winquist (additional)

References 23 Referenced 125

10.1200/JCO.1992.10.8.1245
10.1200/JCO.2005.01.057
10.1200/JCO.2004.06.147
10.1200/JCO.2001.19.4.1088
Grandis JR, Tweardy DJ: Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 53:3579,1993-3584,
Ang KK, Berkey BA, Tu X, et al: Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62:7350,2002-7356,
10.1016/j.ejca.2004.10.014
10.1053/j.seminoncol.2004.09.015
10.1200/JCO.2004.06.075
10.1200/JCO.1992.10.2.257
Pollack VA, Savage DM, Baker DA, et al: Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: Dynamics of receptor inhibition in situ and antitumor effects in athymic mice. J Pharmacol Exp Ther 291:739,1999-748, (10.1016/S0022-3565(24)35162-6)
Agulnik M, da Cunha-Santos G, Hedley D, et al: Predictive and pharmacodynamic biomarker studies in tumor and skin tissue samples of patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated by erlotinib. J Clin Oncol 25:10.1200/JCO.2006.07.6554 (10.1200/JCO.2006.07.6554)
10.1093/jnci/92.3.205
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10.1200/JCO.2001.19.13.3267
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10.1200/jco.2004.22.14_suppl.619
10.1200/jco.2004.22.14_suppl.623

Dates

Type	When
Created	18 years, 3 months ago (May 30, 2007, 6:29 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 16, 2025, 3:09 p.m.)
Indexed	2 months, 4 weeks ago (June 10, 2025, 7:25 p.m.)
Issued	18 years, 3 months ago (June 1, 2007)
Published	18 years, 3 months ago (June 1, 2007)
Published Print	18 years, 3 months ago (June 1, 2007)

Funders 0

None

BibTeX

@article{Siu_2007, title={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}, volume={25}, ISSN={1527-7755}, url={http://dx.doi.org/10.1200/jco.2006.07.6547}, DOI={10.1200/jco.2006.07.6547}, number={16}, journal={Journal of Clinical Oncology}, publisher={American Society of Clinical Oncology (ASCO)}, author={Siu, Lillian L. and Soulieres, Denis and Chen, Eric X. and Pond, Gregory R. and Chin, Soo F. and Francis, Peggy and Harvey, Luc and Klein, Meri and Zhang, Wenjiang and Dancey, Janet and Eisenhauer, Elizabeth A. and Winquist, Eric}, year={2007}, month=jun, pages={2178–2183} }

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