Open AccessDual Inhibition of the Epidermal Growth Factor Receptor Pathway with Cetuximab and Erlotinib: A Phase I Study in Patients with Advanced Solid Malignancies
Author(s) -
Guarino Michael J.,
Schneider Charles J.,
Hosford Martha A.,
Brahmer Julie R.,
Rudin Charles M.,
Finckenstein Friedrich Graf,
PhilipNorton Robyn E.,
Lu Haolan,
Weber Martin R.,
Ettinger David S.
Publication year - 2009
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2008-0124
Subject(s) - medicine , erlotinib , cetuximab , rash , epidermal growth factor receptor , adverse effect , toxicity , mucositis , hypomagnesemia , oncology , lung cancer , egfr inhibitors , erlotinib hydrochloride , pharmacology , cancer , gastroenterology , colorectal cancer , materials science , magnesium , metallurgy
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/m 2 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/m 2 i.v. weekly for cetuximab and 150 mg daily orally for erlotinib.