Bisphosphonates in Oncology: Rising Stars or Fallen Heroes

Abstract

The introduction of bisphosphonates in oncology has dramatically changed the management of patients with metastatic bone disease. In this manuscript, we thoroughly scrutinize the available body of clinical trials supporting the use of bisphosphonates in this setting and review new and ongoing research. Additionally, we summarize the data showing the benefits of bisphosphonate use in the prevention of treatment-induced bone loss and the intriguing emerging evidence on the antitumor potential of some of these agents when used in the adjuvant setting. Finally, we address the need for a careful consideration of potential benefits of bisphosphonate therapy and the risk for osteonecrosis of the jaw, a recently recognized late-toxicity of their use. The Oncologist 2009;14:181-191

Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper

“…Oral clodronate (at the dose of 1,600 mg per day) has been demonstrated to improve BMD at lumbar spine (+2.9%) and femoral neck (+3.7%) in a study on 121 postmenopausal women with breast cancer [79]. Studies with alendronate have been performed on a very small cohort of patients, thus leading to inconclusive results (not significant increase in lumbar spine and hip BMD) [80,81]. The effects of the new human monoclonal antibody denosumab have also been explored.…”

RANK ligand inhibition in bone metastatic cancer and risk of osteonecrosis of the jaw (ONJ): non bis in idem?

“…By consensus, ONJ is defined as the persistence of exposed bone in the oral cavity, despite an adequate treatment for 8 weeks, without local evidence of malignancy and no prior radiotherapy to the affected region [2]. Current data on the prevalence of ONJ originates largely from retrospective cohort studies, suggesting that this complication occurs in approximately 1-10% of bisphosphonate users, with a pooled risk estimate of 2.4% (95% CI, 2.1-2.7%) [3]. However, this number can be reduced with a screening dental visit before the start of therapy and the avoidance of invasive procedures, such as dental extractions [4,5].…”

Nasal septum perforation and bevacizumab

“…It is important that oncologists recognize and report unusual adverse events seen with the use of targeted therapy. Some side effects only become apparent through post-marketing surveillance by pharmaceutical companies and by self-reporting from physicians [11][12][13]. Increased rates of anaphylaxis with the use of cetuximab in specific geographic areas of North America is an appropriate case in point [14].…”

“…The complete side-effect profile of newly licensed drugs may not been seen in pre-approval trials as has been evidenced by several recent cases, i.e., bisphosphonates and osteonecrosis of the jaw, increased cardiovascular risk and rofecoxib, and reactivation of the JC virus resulting in progressive multifocal leukoencephalopathy with the use of natalizumab [11][12][13]. Herein, we report three cases of spontaneous nasal septum perforation secondary to bevacizumab.…”