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

Abstract

Background: Combined therapy of continuous low dosecapecitabine and high dose celecoxib targeting angiogenesiswas used in a phase II trial to treat advancedcancer patients. Dynamic contrast-enhanced magneticresonance imaging (DCE-MRI) was used to monitor antiangiogeniceffects. Material and Methods: 37 Patients(21 men, 16 women), mean age 60 years, with advancedand progressive cancer of various tumor types were included.Therapy consisted of 2 × 500 mg oral capecitabine/day and 2 × 400 mg oral celecoxib/day continuouslyuntil progression of disease. To monitor antiangiogeniceffects, DCE-MRI measurements were performed atbaseline, after 1 month, and after 3 months of therapy.Tumor assessment was performed according to RECISTcriteria, toxicity was evaluated according to the CTC version2.0 catalogue. Results: Therapy was well toleratedwithout grade 3 and 4 toxicities. The mean number oftreatment cycles was 4 (range: 1-15+). Disease stabilizationafter 3 cycles was seen in 11 patients. 6 patientswere stable over long periods. The mean number oftreatment cycles in this group was 10 (range: 7-15+).DCE-MRI demonstrated a reduction of tumor vessel permeabilityand blood flow in patients who reached stabledisease or some minor regression. Conclusion: Continuousdosing of the combination of capecitabine and celecoxibwas well tolerated, produced antiangiogenic effects,and has antitumor activity. Patients with rapid progressiondid not benefit.Metronomic Antiangiogenic Therapy with Capecitabineand Celecoxib in Advanced Tumor Patients - Results of aPhase II StudySimone Steinbild Jann Arends Michael Medinger Brigitte Häring Annette FrostJoachim Drevs Clemens Unger Ralph Strecker Jürgen Hennig Klaus MrossTumor Biology Center at the Albert Ludwigs University Freiburg and MR Development and Application Center of the University HospitalFreiburg, Germany