Clinical Trial Report

Cancer Chemotherapy and Pharmacology

, Volume 62, Issue 4, pp 717-725

First online:

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

  • Alessandra FabiAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer Institute
  • , Giulio MetroAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer Institute
  • , Paola PapaldoAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer Institute
  • , Marcella MottoleseAffiliated withDepartment of Pathology, Regina Elena National Cancer Institute
  • , Elisa MelucciAffiliated withDepartment of Pathology, Regina Elena National Cancer Institute
  • , Paolo CarliniAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer Institute
  • , Isabella SperdutiAffiliated withDivision of Statistics, Regina Elena National Cancer Institute
  • , Michelangelo RussilloAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer Institute
  • , Alain GelibterAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer Institute
    • , Gianluigi FerrettiAffiliated withDepartment of Experimental Medicine and Pathology, University “La Sapienza”
    • , Silverio TomaoAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer InstituteDepartment of Experimental Medicine and Pathology, University “La Sapienza”
    • , Michele MilellaAffiliated withDepartment of Experimental Medicine and Pathology, University “La Sapienza” Email author 
    • , Francesco CognettiAffiliated withDivision of Medical Oncology A, Regina Elena National Cancer Institute

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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.

Keywords

Capecitabine Celecoxib COX-2 Metastatic breast cancer