Phase i study of cetuximab, erlotinib, and bevacizumab in patients with advanced solid tumors

Chia Chi Lin, Emiliano Calvo, Kyriakos P. Papadopoulos, Amita Patnaik, John Sarantopoulos, Alain C. Mita, Glenn G. Preston, Monica M. Mita, Jordi Rodon, Theresa Mays, I. Tien Yeh, Pat O'Rourke, Chris H. Takimoto, Janet E. Dancey, Helen Chen, Anthony W. Tolcher

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: Complex interrelationships exist between the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor pathways. EGFR activation elicits cell proliferation and increased VEGF expression. To maximally inhibit EGFR and then downstream VEGF activity, this phase I study was initiated to determine the maximum tolerated dose (MTD) of erlotinib with fixed-dose cetuximab, and then combine with bevacizumab in patients with advanced malignancies. Patients and methods: Patients with advanced malignancies likely to express EGFR were treated with a full dose of cetuximab intravenous weekly, combined with various doses of oral erlotinib daily (Part 1). Once the MTD was determined in Part 1, escalating doses of bevacizumab were administered intravenously biweekly (Part 2). Results: Forty patients were enrolled and received 155 courses over four dose levels. In Part 1, dose-limiting grade 3 rash occurred in two patients administered with erlotinib at 100 mg daily, and the MTD of erlotinib for this combination was 50 mg daily with standard-dose cetuximab (11 patients treated). Other adverse events included rash, diarrhea, fatigue, and hypomagnesemia. In Part 2, bevacizumab at 10 mg/kg intravenous every 2 weeks was safely added, with additional nondose-limiting headache, proteinuria, and hypertension. There was one partial response in a patient with renal cell carcinoma. Durable stable disease was observed in five patients for 6-11 months. Conclusions: The MTD for Part 1 was 50 mg daily of erlotinib combined with standard cetuximab. Bevacizumab at 10 mg/kg biweekly can be safely administered with the MTD for erlotinib and cetuximab combination.

Original languageEnglish (US)
Pages (from-to)1065-1071
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume63
Issue number6
DOIs
StatePublished - May 1 2009

Keywords

  • Epidermal growth factor receptor
  • Renal cell carcinoma
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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  • Cite this

    Lin, C. C., Calvo, E., Papadopoulos, K. P., Patnaik, A., Sarantopoulos, J., Mita, A. C., Preston, G. G., Mita, M. M., Rodon, J., Mays, T., Yeh, I. T., O'Rourke, P., Takimoto, C. H., Dancey, J. E., Chen, H., & Tolcher, A. W. (2009). Phase i study of cetuximab, erlotinib, and bevacizumab in patients with advanced solid tumors. Cancer Chemotherapy and Pharmacology, 63(6), 1065-1071. https://doi.org/10.1007/s00280-008-0811-x