Clodronate - A review of its use in breast cancer

Like other members of its class, the bisphosphonate clodronate (clodronic a cid) inhibits bone resorption, The efficacy of oral clodronate 1600 mg/day in reducing the incidence of skeletal complications and metastasis developm ent has been assessed in several clinical trials in patients with breast ca ncer, 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 recipie nts in 2. randomised double-blind placebo-controlled studies, each involvin g >100 patients. Significant differences in favour of clodronate were also seen in the frequency of some individual skeletal events in I trial. A nonblind trial in 302 patients considered tube at high risk of developing metastases found that, at a li-ycar follow-up, significantly fewer patient s who received clodronate for 2 years developed skeletal metastases than Ch ose 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 w omen with recurrent breast cancer found that clodronate: significantly decr eased the total number of new skeletal metastases, but not the number of pa tients who developed them. In a nonblind trial in 299 patients with node-positive breast cancer, howev er, the incidence of skeletal metastases did not differ significantly betwe en patients who received clodronate for 3 years and those in a control grou p. In addition, clodronate recipients had a significantly greater incidence of nonskeletal metastases (local and visceral), and significantly lower su rvival rates, Intravenous or oral clodronate has been well tolerated in clinical trials, The most common adverse effects reported were mild gastrointestinal disturb ances such as nausea, vomiting and diarrhoea, All these events were transie nt, and usually resolved without stopping treatment. Conclusions: Clodronate is a well tolerated bisphosphonate, available in bo th oral and intravenous farms, that significantly reduces the incidence of skeletal complications associated with breast cancer. Further research is n eeded to establish more clearly its efficacy in reducing metastasis develop ment, to assess its efficacy compared with other bisphosphonates, and to de termine which patients will benefit most from treatment, Currently, clodron ate is probably most effective in the treatment and prevention of general s keletal complications in patients with breast cancer.