Annals of Oncology Advance Access originally published online on March 2, 2009
Annals of Oncology 2009 20(4):615-620; doi:10.1093/annonc/mdn693
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
reviews |
Role of combination therapy with aromatase and cyclooxygenase-2 inhibitors in patients with metastatic breast cancer
1 Department of Medical Oncology, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
2 Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow, UK
3 Medical Oncology Unit, Oncologisch Centrum Sint-Augustinus, Antwerp, Belgium
* Correspondence to: Dr C. Falandry, Université de Lyon and Hospices Civils de Lyon, EA 3738 and Department of Medical Oncology, Centre Hospitalier Lyon Sud, Pierre-Bénite, France. Tel: +33-478-864-318; Fax: +33-478-86-43-19; E-mail: claire.leger-falandry{at}ens-lyon.fr
Aromatase inhibitors (AIs) are well established in the treatment of metastatic hormone-sensitive breast cancer in postmenopausal women. Cyclooxygenase (COX)-2 inhibitors have demonstrated efficacy in reducing cancer risk in animal and human studies. In several preclinical studies, combination AI plus COX-2 inhibitor therapy has shown a synergistic antitumor effect. This review describes the utility of AI plus COX-2 inhibitor therapy and discusses the completed and ongoing clinical trials investigating treatment with the AI exemestane and the COX-2 inhibitor celecoxib in the neo-adjuvant and metastatic breast cancer settings. In general, combination therapy had comparable or better efficacy compared with AI monotherapy using the end points of progression-free survival, overall response rate, clinical benefit rate, time to progression, and duration of clinical benefit. All therapies were well tolerated. There appeared to be a beneficial impact on serum lipid levels for patients receiving combination therapy in a neo-adjuvant trial despite the known cardiovascular toxicity risk associated with COX-2 inhibitors. In conclusion, AIs plus COX-2 inhibitors have shown promising efficacy and safety for the treatment of patients with metastatic breast cancer. Careful monitoring during future trials will be necessary to accurately assess the risk–benefit ratio of combination therapy.
Key words: adjuvant, advanced breast cancer, aromatase inhibitor, celecoxib, exemestane
Received for publication May 23, 2008. Revision received October 1, 2008. Accepted for publication October 2, 2008.