Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases - Long term follow-up of two randomized, placebo-controlled trials

BACKGROUND. Pamidronate therapy previously has been shown to reduce skeleta l complications effectively for up to 12 months in breast carcinoma patient s with bone metastases. The current study data provide further follow-up re sults regarding the effects of long term (up to 24 months) pamidronate trea tment in women with breast carcinoma and osteolytic metastases. METHODS. Follow-up results from two prospective, multicenter, randomized, d ouble-blind, placebo-controlled intervention trials conducted at academic a nd community oncology centers were combined to provide a large data set wit h which to evaluate the long term efficacy and safety of pamidronate therap y. Seven hundred fifty-four women with Stage IV breast carcinoma and osteol ytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysi s. A total of 751 evaluable patients were randomized to receive either a 90 -mg intravenous pamidronate infusion (367 patients) or a placebo infusion ( 384 patients) every 3-4 weeks. The primary outcome measures were skeletal m orbidity rate (events/year), proportion of patients developing a skeletal c omplication, and time to first skeletal complication. RESULTS. Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 3 84 women who received placebo, 100 (26.0%) completed the study and 76 (19.8 %) discontinued the study due to adverse events. The skeletal morbidity rat e was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001) . In the pamidronate group, 186 of the 367 patients (51%) had skeletal comp lications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Si x patients treated with pamidronate discontinued treatment due to drug-rela ted adverse events. Pain and analgesic scores were significantly worse in t he placebo group compared with those patients in the pamidronate group. CONCLUSIONS. In the current study, monthly infusions of 90 mg of pamidronat e as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal compli cations and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases. (C) 2000 American Cancer Society.