Progress in the treatment and palliation of advanced breast cancer: does the dose of pamidronate determine its effects?

Bisphosphonates are the treatment of choice in tumor-induced hypercalcemia. Pamidronate (Aredia) is effective in this indication, but few studies have addressed the question of its dose-effect relationship. Review of the published literature suggests that a clinically relevant dose-response relationship exists in the dose range 30-60 mg; most hypercalcemic patients will achieve normocalcemia with a dose of 60 mg pamidronate or more. More recent publications have reported the emerging role of bisphosphonates in the treatment of malignant osteolytic bone disease. Several non-randomized studies have shown beneficial effects from continuous administration of clodronate or pamidronate, though the magnitude of such effects was moderate. Two dose escalation trials with pamidronate showed that regimens with a dose intensity below 20 mg/week and single doses of 30 mg or less were ineffective. One randomized, prospective study compared pamidronate 60 mg with 90 mg given intravenously every 3 weeks. Both regimens showed a significant palliative effect. Patients treated with 90 mg had a greater reduction in pain intensity compared to those receiving 60 mg. Optimal schedules for different patient populations require further investigation.