According to results recently published in the European Journal of Cancer, clodronate appears to slow bone loss in pre-menopausal breast cancer patients who are treated with adjuvant chemotherapy.
Breast cancer is a common malignancy with over 200,000 women diagnosed each year in the United States. Patients with localized (cancer confined to the site of origin) or locally advanced (cancer invading nearby tissue or lymph nodes) breast cancer often receive adjuvant chemotherapy (therapy following surgery) in order to improve chances for long-term survival or a cure. However, chemotherapy may stop the ovaries from functioning, resulting in bone loss and an increased risk of developing bone fractures. Researchers are investigating therapeutic options in an attempt to reduce bone loss in women with breast cancer receiving chemotherapy.
Bisphosphonates are a class of drugs that have been demonstrated to prevent bone loss in certain cancers. Although the exact mechanism through which bisphosphonates work is not yet completely understood, research has indicated that bisphosphonates bind to bone and cartilage, which inhibits the biological process that causes the breakdown of bone. In addition, research indicates that bisphosphonates may directly kill osteoclasts (cells responsible for the breakdown of bone). Clodronate is a bisphosphonate that is being evaluated in clinical trials for the prevention of bone loss and the prevention of bone metastases. Results from clinical trials evaluating clodronate in patients with advanced breast cancer have not been consistent; therefore, researchers are continuing clinical trials in order to determine specific disease and/or patient characteristics for which clodronate may be of benefit.
Researchers from Helsinki University Central Hospital in Finland conducted a clinical trial evaluating clodronate in the prevention of bone loss in 73 premenopausal women with breast cancer. All patients were treated with adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy and half of the patients received clodronate for three years. Five years following therapy, bone mineral density was tested in the patient’s spine and hip and compared to pre-treatment results. Patients were divided into two groups; those who had preserved menstruation and those who had stopped menstruating due to treatment. Overall, patients who had preserved menstrual function had significantly greater bone mineral density compared to the patients who had stopped menstruating. Within the group of women who had stopped menstruating, patients treated with clodronate had an average of a 5.8% bone loss of the spine, compared to a 9.7% loss in patients not treated with clodronate. Bone loss of the hip was 3.5% for patients treated with clodronate and 5.1% for patients not treated with clodronate.
The researchers concluded that chemotherapy-induced ovarian failure in pre-menopausal women caused accelerated bone loss of the spine. However, clodronate treatment appeared to significantly reduce the bone loss in these patients, even two years after the termination of treatment. Pre-menopausal breast cancer patients who are receiving adjuvant chemotherapy may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating clodronate or other bisphosphonates. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (cancer.gov) and www.eCancerTrials.com . eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (Vehmanen L, Saarto T, Elomaa I, et al.: Long-term impact of chemotherapy-induced ovarian failure on bone mineral density (BMD) in premenopausal breast cancer patients. The effect of adjuvant clodronate treatment. European Journal of Cancer 2001; 37:2373-2378)
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