A RANDOMIZED, CONTROLLED TRIAL OF INTRAVENOUS CLODRONATE IN PATIENTS WITH METASTATIC BONE-DISEASE AND PAIN

To evaluate the effectiveness of intravenous clodronate in amelioratin g refractory bone pain in patients with metastatic bone disease, 60 pa tients with established asseous metastases and persistent bone pain we re randomized to receive! either clodronate (600 mg or 1500 mg in 500 mt of normal saline) or 500 mt of saline as placebo. After 2 weeks, th e patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorde d throughout the study period Forty-six patients were evaluable (77%). A treatment X period interaction was identified in thc VAS and daily morphine equivalent dose (DMED) scores. First period analysis of thp V AS scores for general pain, pain at rest, and pain upon movement demon strated an average reduction of 13, 14, and 24 mm, respectively from b aseline, but were not significantly different from changes following p lacebo. The average change in DMED was - 6.4 (SE = 2.9) following clod ronate and was + 24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57 %) patients chose clodronate, 12 (26%) chose placebo and eight (17%) h ad no preference (p = 0.0021). For the investigators who also made a b linded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, a nd no difference was apparent in six (13%) (p < 0.0001). intravenous clodronate appeared to have analgesic effect i n patients with refractory bone pain due to metastatic bone disease Th e optimal dose and duration of effect require further evaluation, part icularly in patients with stable disease and persistent bone pain. (C) U.S. Cancer Pain Relief Committee, 1997.