Zolandronic acid protective effect on bone loss in postmenopausal women switched from tamoxifen to letrozole in the treatment of early breast cancer.

Abstract #1153 BACKGROUND: Adjuvant treatment with aromataze inhibitors (AI9s) in postmenopausal women (PMW) with early breast cancer (BC) can be associated with decreased bone mineral density (BMD) and increase risk of osteoporosis and fractures. Tamoxifen on the contrary, increases BMD, and has bone protective effect. Previous studies showed that the addition of Zolandronic (ZA) acid to adjuvant treatment with AI9s reduce bone loss. This study is designed to evaluate the efficacy and safety of ZA in preventing AI9s bone loss in PMW with early BC who are receiving adjuvant Letrozole therapy after Tamoxifen.
 PATIENTS AND METHODS: This is an open-label, randomized phase II. The study enrolled PMW diagnosed and treated for stage I-III hormone receptor positive BC previously treated with Tamoxifen for the last 2.5 years with BMD T- score > -2.5. Patients were randomly assigned to receive Letrozole +/- ZA. Patients on treatment arm received ZA at base-line and every 6 months for 2 years. All patients are being evaluated every 6 months with blood chemistry and BMD test to detect changes in Lumbar and hips BMD and Alkaline phosphatase as serum bone turnover markers (at 6,12,18,24 and 36 months). Letrozole dose was 2.5mg/ daily and ZA 4 mg IV. All patients received supplemental vitamin D and calcium.
 RESULTS: Sixty one patients were screened. Median age was 58.9 years (46.5-83.6), all patients were postmenopausal for at least 12 months, median ECOG performance status was 1 (0-2).). All patients are alive and only one patient had an ipsilateral breast cancer recurrence.
 Fifty eight patients were evaluable (3 pts were screening failure), 26 randomized to receive ZA and 32 to the control group. Four patients withdrew from the protocol.
 Median follow up (FU) is 15.6 months (0.7-41.9), 13 patients had 4 BMD evaluations, 24 had 3 and 39 had 2 (including base-line evaluations). A comparison between groups and between time points was performed by one-way Analysis of Variance with repeated measures using the Mixed model. At this point in time a significant interaction between groups and time trend was found, in favor of ZA treated group in lumbar T score (p=0.0422). While in the control group a significant decline in lumbar BMD was noticed (p= (0.0009, in the treatment group BMD did not change over time (p= 0.9783).
 Adverse events with ZA were mild with some musculoskeletal pain within 2 days post infusion as the most common reported toxicity, one patient had fever and severe pain for 5 days. No serious renal adverse event or ONJ cases were reported. ZA was safe and well tolerated.
 CONCLUSION: Our study reports, a significant benefit in bone mineral density (BMD) when adding Zolandronic Acid to letrozole after switching from Tamoxifen. Letrozole induced bone loss, increases with time and a longer follow up is needed to evaluate the real magnitude of ZA protection effects. Further investigation is warranted. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1153.