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First Published Online January 31, 2009
The Oncologist, Vol. 14, No. 2, 119-124, February 2009; doi:10.1634/theoncologist.2008-0124
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Clinical Pharmacology

Dual Inhibition of the Epidermal Growth Factor Receptor Pathway with Cetuximab and Erlotinib: A Phase I Study in Patients with Advanced Solid Malignancies

Michael J. Guarinoa, Charles J. Schneidera, Martha A. Hosforda, Julie R. Brahmerb, Charles M. Rudinb, Friedrich Graf Finckensteinc, Robyn E. Philip-Nortond, Haolan Lue, Martin R. Webere, David S. Ettingerb

aHelen F. Graham Cancer Center, Christiana Care, Newark, Delaware, USA; bThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; cBristol-Myers Squibb Company, Princeton, New Jersey, USA; dOSI Oncology, Melville, New York, USA; eBristol-Myers Squibb Company, Wallingford, Connecticut, USA

Key Words. Cetuximab • Erlotinib • Phase I • Solid malignancies

Correspondence: Michael J. Guarino, M.D., Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, 4701 Ogletown-Stanton Road, Suite 2200, Newark, Delaware 19713, USA. Telephone: 302-366-1200; Fax: 302-366-1700; e-mail: mguarino{at}cbg.org

Received May 29, 2008; accepted for publication December 1, 2008; first published online in THE ONCOLOGIST Express on January 31, 2009.

Disclosures: Michael J. Guarino: None; Charles J. Schneider: None; Martha A. Hosford: None; Julie R. Brahmer: Consultant/advisory role: Abbott, Cephalon, Genentech, Eli Lilly, AstraZeneca; Charles M. Rudin: Consultant/advisory role: CTI

Pharmaceuticals, Amgen; Research funding/contracted research: Pharmion; Friedrich Graf Finckenstein: Employment/leadership position: Bristol-Myers Squibb; Ownership interest: Bristol-Myers Squibb; Robyn E. Philip-Norton: Employment/leadership position: OSI Pharmaceuticals; Haolan Lu: Employment/leadership position: Bristol-Myers Squibb; Martin R. Weber: Employment/leadership position: Bristol-Myers Squibb; Ownership interest: Bristol-Myers Squibb; David S. Ettinger: Consultant/advisory role: AstraZeneca, Bristol-Myers Squibb; Eli Lilly, GlaxoSmithKline, Merck, MGI Pharma, Pfizer, Sanofi-Aventis; Research funding/contracted research: Bayer, Genentech, Pharmion.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Purpose. To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies.

Patients and Methods. Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m2 i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity.

Results. Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1–31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1–25.1 weeks).

Conclusion. Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m2 i.v. weekly for cetuximab and 150 mg daily orally for erlotinib.






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