Preliminary Study Results Demonstrate that Zoledronic Acid May Have Anti-Tumor Properties

Early evaluations of zoledronic acid, a bisphosphonate used for the treatment of bone metastases in advanced breast cancer, suggest a possible direct anti-tumor effect when combined with neoadjuvant chemotherapy in breast cancer treatment, according to data presented at the CTRC-AACR San Antonio Breast Cancer Symposium. Bisphosphonates may therefore offer an (neo)adjuvant therapeutic strategy of potential importance.

“Zoledronic acid is primarily targeted to bone and metastasis within the bone marrow microenvironment, but it may also be enhancing the response in the primary breast tumor,” said Robert Coleman, M.D., FRCP, professor of medical oncology at the University of Sheffield in the United Kingdom. Coleman is the lead researcher on the AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) trial, which is evaluating the effect of zoledronic acid on breast cancer.

Although the larger AZURE trial is still being evaluated, if the findings in this smaller study are confirmed, the effect could be 'practice changing,' Coleman said. The AZURE trial, a prospective, randomized, open label, clinical trial , enrolled 3,360 women with stage II/III breast cancer to determine whether treatment with zoledronic acid in addition to adjuvant or neoadjuvant chemotherapy would improve disease outcomes. Coleman and colleagues performed a retrospective pathology analysis on 205 patients who received neoadjuvant chemotherapy to determine zoledronic acid’s impact on the primary tumor. Zoledronic acid appeared to reduce tumor size from 30 mm in the chemotherapy alone group to 20.5 mm in the combination group. After adjusting for variables like estrogen receptor status and treatment duration, the difference remained at 42.4 mm in the chemotherapy group and 28.2 mm in the combination group. The pathological complete response rate was 5.8% in the chemotherapy arm and 10.9% in the zoledronic acid group.

The number of patients requiring mastectomy was 77.9% in the chemotherapy group and 65.3% in the combination group. “Zoledronic acid is currently approved for the treatment of bone metastasis and osteoporosis. If the AZURE trial remains positive, then we’ll file for an additional indication,” said Coleman.

For more information

• Winter MC, Thorpe HC, Burkinshaw R, Beevers SJ, Coleman RE, The addition of zoledronic acid to neoadjuvant chemotherapy may influence pathological response exploratory evidence for direct anti-tumor activity in breast cancer. Abstract 5101; SABCS, December 10-14, 2008.