Phase I study of epidermal growth factor receptor (EGFR) inhibitor, erlotinib, and vascular endothelial growth factor monoclonal antibody, bevacizumab, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)

Abstract

5539 Background: Studies of EGFR inhibitors in SCCHN have demonstrated reproducible activity. Preclinical studies have implicated angiogenesis as a mechanism of resistance to these agents. Furthermore, angiogenesis has been linked with tumor progression and worse outcome in SCCHN. This phase I multi-institutional trial was undertaken to assess the feasibility and toxicity of adding bevacizumab, an anti-VEGF monoclonal antibody to erlotinib, an EGFR tyrosine kinase inhibitor. Methods: Eligible patients were required to have performance status 2 or better, measurable disease, intact organ function, no more than one prior therapy for recurrent/metastatic disease, and no prior EGFR or VEGF based therapy. Escalating doses of bevacizumab (5, 10, and 15 mg/kg IV q3 weeks) were administered with a fixed dose of erlotinib (150 mg PO QD) to consecutive patient cohorts to establish a phase II dose. Plasma VEGF and serum TGF-alpha levels were drawn prior to therapy, after 2 weeks, and after 8 weeks of therapy. Results: 10 patients have been enrolled with 4, 3, and 3 patients in each cohort. Grade 3 toxicity consisted of diarrhea (1 patient), skin rash (1 patient), lymphopenia (1 patient). One patient experienced grade 4 hemorrhage from a tongue tumor after 6 treatment cycles that was felt to be therapy related. Common grade 1/2 toxicities observed included dermatologic (70%), fatigue (70%), and diarrhea (50%). Dose limiting toxicity, as defined by the protocol, was not observed at any dose level. Of 9 patients evaluated after 2 cycles, we have observed 1 PR, 7 SD, and 1 PD. 6 patients have had stable disease for greater than 12 weeks. Conclusions: Administration of bevacizumab 15mg/kg q3 weeks with erlotinib 150mg QD is feasible and well tolerated in recurrent/metastatic SCCHN. Assessment of regimen efficacy is underway in the phase II segment of this trial. Supported by NCI grant # N01-CM-17102. No significant financial relationships to disclose.