Long-term safety and efficacy of bisphosphonate (BP) therapy for more than 24 months (M) in breast cancer (BC) patients (pts) with bone metastasis (BM)

Abstract

816 Background: In BC pts, bone is the most frequent site of distant metastasis. BPs exhibit highly beneficial effects on lytic bone lesions in BC pts. ASCO guidelines on the role of BPs in women with BC suggest that intravenous BPs be continued until evidence of substantial decline in general performance status (PS). However, the safety of continuing BP therapy for a prolonged period has rarely been investigated. We studied the long-term safety and efficacy of BP therapy in BC pts with BM who received BP therapy for more than 24 M as long-term administration. Methods: Pamidronate (PMT) 45mg and incadronate (INC) 10mg were given over 60 min intravenous infusion to BC pts with BM. The dosing interval was every 2 weeks at the start. When an effective response was obtained, BP was given at the interval of every 4 weeks or longer. PMT was given to all pts at the start, then changed to INC when there was no response. All pts received systemic therapy. Laboratory tests were performed at every administration. Adverse events (AEs) were assessed using NIC-CTC. Results: Twenty-one pts received BPs for more than 24 M. Median duration of administration of BPs was 48 M (24∼87 M), and 10 pts received BPs for more than 50 M. Eight pts were changed from PMT to INC. During treatment, there were no pathological fractures observed. No radiation or surgical treatment of bone was performed. Hypercalcemia was detected in 1 pt (4.8%). Lytic bone lesions changed to sclerotic lesions in 13 pts (61.9%). Improvement of PS was detected in 7 pts (33.3%). Hypocalcemia was seen in 13 pts (61.9%) but was not symptomatic. Leukopenia, thrombocytopenia and anemia were not observed. The baseline serum creatinine level was maintained and G1 serum creatinine elevation was seen in 4.8% of pts. G1 fatigue (19.0%), fever (13.3%), headache (4.8%) and diarrhea (4.8%) were detected. Major AEs were mild and transient. Conclusions: Severe AEs of long-term BP therapy were not seen. We conclude that long-term BP therapy was very effective and well-tolerated in BC pts with BM. AEs in this study were fewer than in previous reports. The optimal dose, duration and dosing interval for long-term BP therapy should be determined. No significant financial relationships to disclose.