Metronomic antiangiogenic therapy with capecitabine and celecoxib in advanced tumor patients--results of a phase II study

Onkologie. 2007 Dec;30(12):629-35. doi: 10.1159/000110580. Epub 2007 Nov 30.

Abstract

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 x 500 mg oral capecitabine/ day and 2 x 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Angiogenesis Inhibitors / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Celecoxib
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives*
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / drug therapy*
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Deoxycytidine
  • Capecitabine
  • Celecoxib
  • Fluorouracil