Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: Results of a phase II study with biomarker evaluation

Alessandra Fabi, Giulio Metro, Paola Papaldo, Marcella Mottolese, Elisa Melucci, Paolo Carlini, Isabella Sperduti, Michelangelo Russillo, Alain Gelibter, Gianluigi Ferretti, Silverio Tomao, Michele Milella, Francesco Cognetti

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Preclinical evidence suggests that the cyclo-oxygenase-2 (COX-2) enzyme plays an important role in breast cancer progression. The aim of the present phase II study was to determine the activity and safety of the combination of the COX-2 inhibitor celecoxib with capecitabine in metastatic breast cancer (MBC) patients pretreated with anthracyclines and/or taxanes. Methods: Eligible patients received capecitabine 1,000 mg/m2 twice daily on days 1-14 every 21 days and celecoxib 200 mg twice daily, continuously, until disease progression or unacceptable toxicity. Results: About 42 pretreated MBC patients were enrolled into the study. Median number of previous chemotherapy lines for metastatic disease was 2 (0-3). Seven patients (19%) responded to treatment while disease stabilization occurred in 17 patients (40.5%). Overall, 20 patients (47.5%) achieved clinical benefit [objective responses (CR) plus stable disease (SD) ≥6 months]. Median time to progression (TTP) and median overall survival (OS) were 5.2 and 17.8 months, respectively. Treatment was very well tolerated: grade 3 toxicities were observed in only five patients, respectively, and no grade 4 adverse events were reported. Celecoxib was never discontinued for toxicity. Analysis of COX-2 expression in the 22 patients with available tissue revealed a significantly longer TTP and OS for patients whose tumors over-expressed COX-2. Conclusions: The combination of capecitabine and celecoxib is active and safe in far advanced MBC patients. Interestingly, this association resulted in a lower-than-expected toxicity, as compared to single-agent capecitabine. The clinical relevance of COX-2 as determinant of sensitivity to treatment with celecoxib should be further evaluated in larger series of patients.

Original languageEnglish
Pages (from-to)717-725
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume62
Issue number4
DOIs
Publication statusPublished - Sep 2008

Keywords

  • Capecitabine
  • Celecoxib
  • COX-2
  • Metastatic breast cancer

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

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