Originally published as JCO Early Release 10.1200/JCO.2006.05.9212 on September 25 2006

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Phase II Trial Evaluating the Palliative Benefit of Second-Line Zoledronic Acid in Breast Cancer Patients With Either a Skeletal-Related Event or Progressive Bone Metastases Despite First-Line Bisphosphonate Therapy

Mark J. Clemons, George Dranitsaris, Wei S. Ooi, Geetha Yogendran, Tatjana Sukovic, Betty Y.L. Wong, Sunil Verma, Kathleen I. Pritchard, Maureen Trudeau, David E.C. Cole

From the Division of Medical Oncology, Princess Margaret Hospital; Division of Medical Oncology; Department of Clinical Pathology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada

Address reprint requests to Mark J. Clemons, MD, Princess Margaret Hospital (Suite 5-205), 610 University Avenue, Toronto, Ontario, Canada M5G 2M9; e-mail: Mark.Clemons{at}uhn.on.ca

PURPOSE: This study evaluated whether additional palliative benefits could be derived from the second-line use of the more potent bisphosphonate zoledronic acid in metastatic breast cancer patients with either progressive bone metastases or skeletal-related events (SRE), despite first-line therapy with either pamidronate or clodronate.

PATIENTS AND METHODS: This prospective study evaluated the impact of second-line zoledronic acid on pain, quality of life, and markers of bone turnover (for example, urinary N-telopeptide [NTX]). Patients received monthly zoledronic acid (4mg) for 3 months. Study evaluations were made weekly during the first month and again at week 8. No changes in chemotherapy or endocrine therapy were allowed in the month before or after commencing study treatment.

RESULTS: Thirty-one women completed this study. By week 8, patients had experienced significant improvements in pain control (P < .001). There was a downward trend in urinary NTX levels over the same time period (P = .008). Overall, there was a trend towards a positive correlation between improvement in pain control and reduction in week one urinary NTX relative to baseline (Spearman's rho r = 0.27; P = .15).

CONCLUSION: This is the first study to demonstrate that patients with either progressive bone metastases or SREs while on clodronate or pamidronate can have relevant palliative benefits with a switch to the more potent bisphosphonate zoledronic acid. This is reflected by significant improvements in pain control and bone turnover markers. If confirmed in randomized trials, these findings have major implications to the use of bisphosphonates in both the metastatic and adjuvant settings.

published online ahead of print at www.jco.org on September 25, 2006.

Supported in part by the Canadian Breast Cancer Foundation, Ontario Chapter. Laboratory studies (T.S., B.Y.L.W., D.E.C.C.) were supported in part by a grant from the Dairy Farmers of Canada.

Presented in part in poster format at the 28th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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