Like other members of its class, the
bisphosphonate clodronate (
clodronic acid) inhibits
bone resorption. The efficacy of oral
clodronate 1600 mg/day in reducing the incidence of skeletal complications and
metastasis development has been assessed in several clinical trials in patients with
breast cancer. Long term use of oral
clodronate significantly reduced the total cumulative incidence of skeletal events (including fractures, hypercalcaemia, and the need for
radiotherapy for bone
pain) compared with that in placebo recipients in 2 randomised double-blind placebo-controlled studies, each involving >100 patients. Significant differences in favour of
clodronate were also seen in the frequency of some individual skeletal events in 1 trial. A nonblind trial in 302 patients considered to be at high risk of developing
metastases found that, at a 3-year follow-up, significantly fewer patients who received
clodronate for 2 years developed skeletal
metastases than those in a control group.
Clodronate recipients were also significantly less likely than controls to develop visceral
metastases, and had significantly higher survival rates. A smaller double-blind placebo-controlled study in women with recurrent
breast cancer found that
clodronate significantly decreased the total number of new skeletal
metastases, but not the number of patients who developed them. In a nonblind trial in 299 patients with node-positive
breast cancer, however, the incidence of skeletal
metastases did not differ significantly between patients who received
clodronate for 3 years and those in a control group. In addition,
clodronate recipients had a significantly greater incidence of nonskeletal
metastases (local and visceral), and significantly lower survival rates. Intravenous or oral
clodronate has been well tolerated in clinical trials. The most common adverse effects reported were mild gastrointestinal disturbances such as
nausea,
vomiting and diarrhoea. All these events were transient, and usually resolved without stopping treatment.
CONCLUSIONS:
Clodronate is a well tolerated
bisphosphonate, available in both oral and intravenous forms, that significantly reduces the incidence of skeletal complications associated with
breast cancer. Further research is needed to establish more clearly its efficacy in reducing
metastasis development, to assess its efficacy compared with other
bisphosphonates, and to determine which patients will benefit most from treatment. Currently,
clodronate is probably most effective in the treatment and prevention of general skeletal complications in patients with
breast cancer.