Clodronate as a Single-dose Intravenous Infusion Effectively Provides Short-term Correction of Malignant Hypercalcemia

Abstract

The efficacy and safety of a single intravenous (I.V.) infusion of clodronate 1 500 mg or 900 mg was compared with a single I.V. infusion of pamidronate 90 mg in the treatment of malignant hypercalcemia. Primary efficacy data from two separate, but parallel, randomized double-blind controlled multi-center studies (N=63), involving patients with malignant hypercalcemia (S-Ca_cor>2.68 mmol/l), were pooled along with results from a study (N=4), in which an open I.V. phase was followed by a randomized oral phase. The primary efficacy variable, the proportion of normocalcemic patients at day 5 could be evaluated from 51 subjects. Of them, 21 were in the clodronate 1 500 mg group, 10 in the clodronate 900 mg group and 20 in the pamidronate 90 mg group. After the rehydration, the patients were given a single I.V. infusion of clodronate 1 500 mg, clodronate 900 mg or pamidronate 90 mg. The patients were followed up for five days and S-Ca_corwas measured daily. At day 5, a total of 16 patients (76%) in the clodronate 1 500 mg group, six patients (60%) in the clodronate 900 mg group and 17 patients (85%) in the pamidronate 90 mg group were normocalcemic, the differences between the treatment groups being statistically non-significant. The differences in the mean S-Ca_corbetween the treatment groups were statistically non-significant. I.V. clodronate given either as 900 mg or 1 500 mg single-dose was safe and well tolerated.