One hundred forty-four patients with
breast cancer and osteolytic bone
metastases were randomized to receive either oral
clodronate 1,600 mg/d (73 patients) or placebo (71 patients), in addition to either
chemotherapy or hormonal
therapy, for up to 12 months. Patients were withdrawn from the study when the 12 months of treatment had been achieve or a new bone event occurred, which was defined as:
hypercalcemia (> 3 mmol/l), increase in, or onset of new bone
pain due to
metastases, requirement of
radiotherapy for bone
pain relief,
pathological fractures (including vertebral collapse,
spinal cord compression) or death due to bone
metastases. Patients are well balanced according to age, performance status, bone condition, except for fractures, more frequent in the
clodronate group (25% vs 12%). Of the 137 evaluable patients, 69 received oral
clodronate and 68 placebo.
Clodronate significantly delayed the median time to onset of new bone events compared to placebo, respectively 244 days and 180 days (p = 0.05).
Hypercalcemia did not occur in the
clodronate group but was observed in four placebo-treated patients.
Clodronate-treated patients had a significant reduction in
pain intensity compared to placebo (p = 0.01; measured using a visual
pain scale) and significantly fewer patients receiving
clodronate required
analgesics (p = 0.02). The evaluation of global efficacy by physicians and patients indicated that
clodronate was more efficacious than placebo (respectively p = 0.02 and p = 0.01). No significant difference in incidence of adverse effects was observed between the two groups.
Clodronate therapy significantly delayed the occurrence of new bone events in these patients with bone
metastases from
breast cancer and adds to treatment of malignant
osteolysis.