Effect of pamidronate on skeletal morbidity in myelomatosis. Part 1. The results of the first 12 months of pamidronate therapy

Osteolytic bone destruction caused by increase of osteolytic activity is a major manifestation of multiple myeloma (MM). Pamidronate (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate) inhibits osteoclastic activity and reduces bone resorption. Since October 1995 the efficacy of pamidronate is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. 46 patients with stage III myeloma and osteolytic lesions were randomized to receive either pamidronate (Aredia; Novartis) 60 mg i.v. in 4-hour infusion monthly (n = 23) or chemotherapy alone (control group n = 23). Estimation of performance status, quality of life, pain score, analgesic consumption, serum calcium concentration and twenty four-hours Calcium excretion, urine Calcium/creatinine ratio is done at least once a month (before pamidronate administration) while X-ray skeletal survey--before treatment and then every six months. In the first months of treatment apparent reduction of bone pain occurred. Hypercalcaemia was revealed in 6 patients at entry into the study. In 5 of these patients pamidronate restored and maintained normocalcaemia for a median 6 months. In 3 patients an aggressive plasma cell proliferation was accompanied by reoccurrence of hypercalcaemia. At skeletal X-ray examination performed after 6 and 12 cycles of pamidronate and by comparing each of consecutive imaging with previous one the progression of osteolysis was respectively found in 67% and 39% of patients. In the control group corresponding figures were: 79% and 70%. The mean number of skeletal events (pathologic fracture, radiation to bone and spinal cord compression) per year was lower in the pamidronate group (1.82) than in control-patients (2.72), p < 0.013. The proportion of patients who developed skeletal event (excluding vertebral fractures) was lower in the pamidronate group -34% v 52%. Adverse events of pamidronate: hypocalcaemia (< 2 mmol/l) observed in 7 patients occurred in particular patients beginning from 2 to 7 days after drug administration. In 2 patients hypocalcaemia that appeared in 24 hours after drug infusion was accompanied by blood pressure decrease; in one case systolic blood pressure dropped up to 60 mmHg, in the other one--to 90 mmHg. Muscular pain and fever up to 39 degrees C (transient and self-limiting "influenza like syndrom") occurred in 5 patients, in two patients after several hours and in three other--after some dozens of hours from drug administrat