Preclinical and Clinical Efficacy of the Bisphosphonate Ibandronate in Cancer Treatment

Frieder      Bauss; Bengt      Bergstrom

Abstract

Bisphosphonates, like ibandronate (Bondronat®), represent the mainstay of treatment for metastatic bone disease. Ibandronate selectively binds to bone mineral and prevents osteoclast-mediated skeletal destruction. This review describes the preclinical and clinical profiles of ibandronate for treatment of cancer metastatic to bone. In preclinical studies ibandronate reduced metastatic processes and tumor growth, induced tumor cell apoptosis, decreased bone pain, and enhanced biomechanical indices. Skeletal destruction was completely prevented with ibandronate, and this directly correlated with histomorphometry and markers of bone turnover. Ibandronate efficacy in combination with anticancer therapies is discussed. Preclinical studies demonstrated that ibandronate does not compromise safety, including renal health. Intravenous and oral ibandronate had comparable efficacy in three Phase III clinical trials. Ibandronate achieved significant risk reductions in the incidence of skeletal-related events and bone pain. In additional clinical studies, ibandronate reduced markers of bone turnover. Furthermore, loading-dose ibandronate rapidly reduced bone pain in Phase II trials. Adjuvant trials are ongoing. The clinical safety profile (including a 4-year follow-up study) has demonstrated renal health is maintained with ibandronate. Overall, ibandronate preserves skeletal integrity, has a favorable safety profile, maintains renal function, and can rapidly reduce and maintain bone pain below baseline levels in patients with cancer metastatic to bone.

Keywords: Ibandronate, bisphosphonates, cancer treatment, bone metastases, bone pain