PAMIDRONATE FOR PAIN CONTROL IN PATIENTS WITH MALIGNANT OSTEOLYTIC BONE-DISEASE - A PROSPECTIVE DOSE-EFFECT STUDY

In a prospective dose-escalation study tolerability and effectiveness of repeated infusions with intravenous pamidronate were investigated. A total of 80 patients with proven malignancy and pain due to osteolyt ic bone disease were enrolled. Doses of 30 mg, 45 mg, 60 mg and 90 mg pamidronate, given every 4 weeks, 3 weeks or 2 weeks were tested. Thus dose intensity was increased by giving higher doses and/or by shorten ing the intervals. A combined palliation score on the bases of pain sc ore (WHO), analgesic score (WHO) and improvement of performance status (SAKK/ECOG) was rated by the physician on a six-point scale. Regressi on analysis showed a close correlation between dose intensity and effe ct (Pearson's R = 0.7: P<0.0001). A statistically significantly differ ent palliation score for patients treated with low (below 15 mg/week), medium (16-30 mg/week) and high doses (above 31 mg/week) of pamidrona te was found (P= <0.01). A dose intensity below 10 mg pamidronate/week and single doses of 30 mg had no clinically relevant benefit, whereas dose intensities of 25-45 mg/week showed a significant palliative eff ect. We conclude that pamidronate should be given in a close intensity of 20 mg per week or more in patients with far advanced osteolytic bo ne disease. Best results are obtained with high doses of 60 mg or 90 m g pamidronate. Further investigations by prospective randomized trials arc needed to determine the optimal dose and schedule of pamidronate infusions.