DELAY IN PROGRESSION OF BONE METASTASES IN BREAST-CANCER PATIENTS TREATED WITH INTRAVENOUS PAMIDRONATE - RESULTS FROM A MULTINATIONAL RANDOMIZED CONTROLLED TRIAL

Purpose: Bone metastases are a major cause of morbidity in breast canc er, resulting in complications that include pain, loss of mobility, pa thologic fracture, and tumor-induced hypercalcemia (TIH). Inhibition o f osteoclast-mediated bone destruction using bisphosphonates represent s a promising new management approach. Patients and Methods: Breast ca ncer patients with bone metastases were randomly allocated to receive chemotherapy alone (152 patients) or chemotherapy plus pamidronate 45 mg in 250 mL of saline as a 1-hour intravenous infusion every 3 weeks (143 patients). Whenever possible, treatment continued until progressi on of disease (PD) in bone appeared on radiographs or bone scan. Time to PD in bone and pain reduction according to a self-assessment six-po int scale were selected as primary end points. PD in bone was verified during extramural review (EMR) of all imaging studies by blinded obse rvers, and these data were used as the main efficacy criterion. Analge sic intake, World Health Organization (WHO) performance status, and co mplications of bone metastases (radiotherapy, TIH, fractures, orthoped ic surgery) were also compared in the two groups. Results and Conclusi on: At EMR, median time to PD in bone increase by 48% in patients who received pamidronate (249 v 168 days; P = .02, Wilcoxon test). Marked pain relief, defined as a two-point decrease lasting for greater than or equal to 6 weeks, was reported by 44% of pamidronate patients and b y 30% of controls (P = .025, chi(2) test). The infusions (median, nine per patient; range, 0 to 39) were well tolerated, with no major toxic ities reported. Pamidronate by repeated infusion can significantly slo w the progression of bone metastases and reduce attendant morbidity. ( C) 1996 by American Society ol Clinical Oncology.