Bisphosphonates Review

The use of bisphosphonates, which reduce the activity of bone-absorbing cells and hence preventing bone thinning, reduces bone problems and bone pain in patients in whom breast cancer has spread to the bone, according to a recent review by Pavlakis et al. that included 21 studies.

As bone is a common site of spread in breast cancer, bone metastasis (cancer spreading to the bone) is a significant cause of illness and death among patients with this malignancy. The aim of the review was to assess the effect of bisphosphonates on skeletal events (bone problems, e.g. fracture), bone pain, quality of life and survival in women with early and advanced breast cancer. Randomised trials were identified and evaluated, comparing different bisphosphonates as well as the use of bisphosphonates with treatment without bisphosphonates. Data extracted from published papers were reviewed for each of the specified endpoints (skeletal events, bone pain, quality of life and survival), using numerical ratings to report skeletal events and survival while subjective qualitative ratings to summarise pain and quality of life.Of the total of 21 studies included, 9 studies involved women with advanced breast cancer and existing bone metastases. In these 9 studies, bisphosphonates reduced the risk of developing a skeletal event by 17%. Of the currently available bisphosphonates, 4 mg IV zolendronate reduces the risk of developing a skeletal event by 41%, while 90 mg IV pamidronate achieved a reduction of 33%. A 18 % reduction was reported for 6 mg IV ibandronate. Skeletal events were reduced by 14 % by 50mg oral ibandronate and 16 % by 1600 mg oral clodronate. Compared with placebo or no bisphosphonate, the skeletal event rate in the presence of bisphosphonate treatment was lower in all of 12 studies in women with clinically evident bone metastases. Delays to the development of bone problems were also demonstrated with the use of intravenous or oral bisphosphonates (intravenous zolendronate, pamidronate and oral clodronate). In terms of bone pain, significant improvement has also been reported in 7 studies (90 mg iv pamidronate, 4 mg iv zolendronate, 6 mg iv ibandronate, 1600 mg oral clodronate and 50 mg oral ibandronate). Survival, however, does not appear to be affected by treatment with bisphosphonate in women with advanced breast cancer. Improvement in global quality of life was reported in only the 3 studies of ibandronate. In early breast cancer, there was no significant effect from the use of bisphosphonate on the development of bone metastasis. Adverse effects are not common, and include gut reactions, transient fever and low calcium level, depending on which drug is used. Mild gut reaction is seen with oral clodronate and oral ibandronate. Kidney toxicity is only seen with 8mg and >15-minute infusion of intravenous zolendronate.In women with advanced breast cancer and clinically evident bone metastases (shown on plain X-ray and/or bone scans), the use of bisphosphonates (oral or intravenous), in addition to standard cancer treatment, is effective in reducing the risk and rate of developing a bone problem as well as increasing the time to a skeletal event (delaying the occurrence of a bone problem). With the use of some bisphosphonates, reduction of bone pain and improvement in global quality of life is also demonstrated. However, the best timing of starting the treatment and its effectiveness in early breast cancer remains a question and requires further research.(Source: Bisphosphonates for breast cancer, The Cochrane Library 2005, Issue 3)