Clodronate: a review of its use in breast cancer

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.

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.