Phase I study of combination treatment with PTK 787/ZK 222584 (PTK/ZK) and cetuximab for patients with advanced solid tumors: Safety, pharmacokinetics, pharmacodynamics, and toxicity analysis

2575 Background: Based on the current knowledge of tumor biology there is a rationale to combine targeted therapies that block different growth factor pathways. Here we combined PTK/ZK, a small molecule inhibitor of all three vascular endothelial growth factor receptors, PDGFR and c-kit, with cetuximab, a monoclonal antibody against the epidermal growth factor receptor. Methods: In this phase I study patients were treated with PTK/ZK daily (cohort 1; 750 mg od, cohort 2; 1250 mg od, cohort 3; 250 mg [morning] and 500 mg [evening], cohort 4; 500 mg [morning] and 750 mg [evening]) combined with cetuximab 250mg/m2 weekly in cycles of 28 days in cohorts of 3 patients. Toxicity was evaluated conform CTCAE classification version 3.0. Pharmacokinetics and circulating endothelial (progenitor) (CE(P)) cell analysis by flow cytometry were performed. Response was assessed using RECIST criteria. Results: Safety and tolerability were evaluated in 16 out of 18 treated patients (median age 61, range 43–78) with advanced...