Metronomic Antiangiogenic Therapy with Capecitabine and Celecoxib in Advanced Tumor Patients – Results of a Phase II Study

Background: Combined therapy of continuous low dose capecitabine and high dose celecoxib targeting angiogenesis was used in a phase II trial to treat advanced cancer patients. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to monitor antiangiogenic effects. Material and Methods: 37 Patients(21 men, 16 women), mean age 60 years, with advanced and progressive cancer of various tumor types were included. Therapy consisted of 2 × 500 mg oral capecitabine/day and 2 × 400 mg oral celecoxib/day continuously until progression of disease. To monitor antiangiogenic effects, DCE-MRI measurements were performed at baseline, after 1 month, and after 3 months of therapy. Tumor assessment was performed according to RECIST criteria, toxicity was evaluated according to the CTC version 2.0 catalogue. Results: Therapy was well tolerated without grade 3 and 4 toxicities. The mean number of treatment cycles was 4 (range: 1-15+). Disease stabilization after 3 cycles was seen in 11 patients. 6 patients were stable over long periods. The mean number of treatment cycles in this group was 10 (range: 7-15+). DCE-MRI demonstrated a reduction of tumor vessel permeability and blood flow in patients who reached stable disease or some minor regression. Conclusion: Continuous dosing of the combination of capecitabine and celecoxib was well tolerated, produced antiangiogenic effects,and has antitumor activity. Patients with rapid progression did not benefit. Metronomic Antiangiogenic Therapy with Capecitabine and Celecoxib in Advanced Tumor Patients - Results of a Phase II Study Simone Steinbild Jann Arends Michael Medinger Brigitte Häring Annette Frost Joachim Drevs Clemens Unger Ralph Strecker Jürgen Hennig Klaus Mross Tumor Biology Center at the Albert Ludwigs University Freiburg and MR Development and Application Center of the University Hospital Freiburg, Germany