The role of bisphosphonates in the management of advanced cancer with a focus on non-small-cell lung cancer. Part 1: Mechanisms of action, role of biomarkers and preclinical applications.
With recent advances in cancer management, patients with metastatic bone disease are likely to have a prolonged clinical course, with skeletal-related events such as pain, hypercalcemia, pathologic fractures, spinal cord and nerve compression. Bisphosphonate use has resulted in the reduction of skeletal-related complications for a number of tumors including breast, prostate and myeloma, and improvements in the quality of life for patients. There is now evidence that newer, highly potent, nitrogen-containing bisphosphonates reduce skeletal complications in patients with bone metastases from other solid tumors (including lung cancer). The early identification of patients at high risk for developing bone metastases may help curtail a complex and costly clinical problem--skeletal-related events. In this article, we review the different mechanisms of bisphosphonates and the potential role of newer-generation bisphosphonates, such as zoledronic acid, in the management of advanced, metastatic bone disease. We include a review of mechanistic studies and preclinical data. Additionally, the utility of evolving concepts such as bone markers and imaging of bone metastases are discussed.
Saba
Nabil
N
Winship Cancer Institute, Emory University, Atlanta, Ga., USA. nabil_saba@emory.org
Khuri
Fadlo
F
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000517:prevention & control / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D004002:Clodronic Acid / Q000627:therapeutic use; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D012968:Etidronic Acid / Q000627:therapeutic use; D005188:False Negative Reactions; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D000077268:Pamidronate; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D013810:Therapeutic Equivalency; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D019788:Fluorodeoxyglucose F18; C058651:tiludronic acid; D000077211:Zoledronic Acid; D012968:Etidronic Acid; D000077268:Pamidronate; D000077557:Ibandronic Acid