HIGH-DOSE INTRAVENOUS PAMIDRONATE FOR METASTATIC BONE PAIN

The bisphosphonates are able to relieve pain from metastatic bone disease and, when given intravenously, may promote bone healing of lytic metastases. In this study, the aim was to assess the acute effects of a single 'high-dose' intravenous treatment with pamidronate on pain, mobility, analgesic consumption and quality of life (QOL). Thirty-four normocalcaemic patients with painful progressing bone metastases (22 from breast, five prostate and seven others) received a single intravenous infusion of 120 mg of pamidronate as palliative therapy. No other systemic therapy or drugs known to influence bone metabolism were administered during the study. Patients' subjective response to treatment was assessed weekly with a pain questionnaire recording a composite of pain intensity, mobility, performance status and analgesic consumption. In addition, patients completed the Rotterdam Symptom Check List (RSCL) for measurement of QOL and a mobility questionnaire. The mean reduction in the pain questionnaire score (recorded on at least two occasions) was 25% [standard error (s.e.) 3%, range 0-75%]. Twenty patients (59%) showed a greater than or equal to 20% improvement and were classified as responders. The median duration of symptomatic response was 12 (range 4-24 +) weeks. The responding patients showed a reduction in RSCL score (improvement in QOL) from 35% before treatment to 27% at 6 weeks, but no significant improvement was noted in non-responders. Twenty-one patients were retreated with pamidronate when their symptoms deteriorated again. Eight out of 15 responders showed a second reduction in pain score of greater than or equal to 20%, but this was not seen in any of the six non-responders. Five patients have remained well with no additional treatment for their disease other than repeat infusions of pamidronate every 3-6 months. Treatment was well tolerated. Eight (24%) experienced fever after the first treatment only, and four had asymptomatic, biochemical evidence of hypocalcaemia. The acute inhibition of osteoclastic bone resorption induced by a single high-dose treatment with pamidronate can provide useful palliation for patients with bone metastases. Responding patients may be retreated as symptoms dictate to good effect. We are currently running a phase III double-blind trial with high-dose pamidronate for progressive painful metastatic bone disease to exclude any placebo effect and observer bias.