Zoledronic acid helps reduce the spread of breast cancer by preventing chemotherapy-related bone loss

March 31, 2010

Zoledronic acid, a bone strengthening drug, given together with chemotherapy might decrease the spread of cancer in women with locally advanced breast cancer by reducing the likelihood of tumour cells growing in bone marrow and spreading to other parts of the body, finds an Article published Online First in The Lancet Oncology.

About 25% of breast cancers spread to the bone first. Bone marrow is a sanctuary for disseminated tumour cells (DTCs) released from the primary tumour where they adapt and spread to other organs. Research has shown that women with DTCs in their bone marrow are at increased risk of developing distant disease and death.

Previous studies have shown that chemotherapy increases rates of bone turnover, which releases bone-derived growth factors which could promote tumour growth in women with breast cancer. It has been suggested that zoledronic acid, a bisphosphate that reduces bone loss by slowing down the activity of cells that destroy bone, has the potential to alter the microenvironment making it less favourable for cancer cells and could result in a decrease in metastatic disease.

Rebecca Aft from Washington University School of Medicine, USA, and colleagues did a randomised phase 2 trial to examine the effects of zoledronic acid on DTCs in women undergoing chemotherapy for locally advanced breast cancer.

120 women were randomly assigned to 4 mg zoledronic acid every 3 weeks for one year starting with their first dose of chemotherapy, or to chemotherapy alone (no zoledronic acid). Bone marrow samples were taken at the start of the study and again at 3 months and 1 year after treatment. 45.7% of patients had detectable tumour cells in their bone marrow at the start of the study.

Findings showed that women who were given zoledronic acid had fewer detectable tumour cells after three months of treatment compared to women who received chemotherapy alone (30% vs 47%).

Of the women who started the study with no tumour cells in their bone marrow, 87% in the zoledronic acid group remained free of tumour cells at 3 months compared to 60% in the group who received chemotherapy alone. One year after treatment, there was no significant difference in the number of patients with detectable tumour cells in their bone marrow between the two groups (40% for zoledronic acid vs 33% for chemotherapy alone).

Additionally, zoledronic acid was effective at preventing treatment-related bone loss at one year. 44% of women with mild osteopenia (low bone mineral density) at the start of the study had normal bone-mineral density after one year of treatment with zoledronic acid and significant decreases in bone-turnover markers at 3 months and one year after treatment.

Zoledronic acid was generally well tolerated with no differences in side effects between the two treatment groups. The most common serious adverse events were infection and thrombosis. One case of osteonecrosis of the jaw was reported in the zoledronic acid group.

The authors say: "Zoledronic acid has antimetastatic properties within the bone marrow and systemically."

They suggest that: "Chemotherapy leads to increased bone turnover and the release of growth factors, providing a favourable environment for DTCs, and that this effect is abrogated by treatment with bisphosphonates."

They call for future studies to address the optimum timing of administration, dose, and target population of bisphosphonate treatment in patients with breast cancer.
Dr Rebecca Aft, Washington University School of Medicine, St Louis, USA. T) +1 314 747 0063 E) aftr@wustl.edu

For full Article see: http://press.thelancet.com/tloaft.pdf


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