Treatment of bone metastases in lung cancer: the actual role of zoledronic acid.
ABSTRACT Approximately 30-40% of NSCLC patients develop bone metastases. Bone metastases are associated with a significant increase in skeletal-related events (SREs), including severe bone pain, hypercalcemia, pathological fractures, spinal cord compression. These SREs result in impaired mobility, reduced quality of life, and frequently require therapeutic intervention (radiation therapy, surgery and systemic treatments). The normal balance of formation of new bone by osteoblasts and the resorption of old bone by osteoclasts becomes imbalanced and/or uncoupled, leading to the development of lesions that are osteolytic, osteoblastic, or a combination of both. The current National Comprehensive Cancer Network (NCCN) Clinical Practice Giudelines in Oncology recommend palliative external-beam radiotherapy for the treatment of bone metastases in patients with NSCLC and healthcare professionals treating such patients are urged to consider bisphosphonate therapy. Zoledronic acid is the first and only bisphosphonate that has proven efficacy for the treatment of bone metastases from a broad range of solid tumor types, including lung cancer.
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ABSTRACT: Paraneoplastic syndromes occur commonly in patients with lung cancer, especially cancers of neuroendocrine origin. The syndromes can be the first clinical manifestation of malignant disease or a harbinger of cancer recurrence. To update the knowledge that would facilitate the care of lung cancer patients with paraneoplastic syndromes, this review focuses on the epidemiology, pathogenesis, clinical features, and current management of the more common and clinically relevant syndromes. Certain combinations of clinical signs and symptoms (endocrine, neurologic, immunologic, dermatologic, metabolic, constitutional, and hematologic) are associated with lung carcinoma as a manifestation of the secretion of cytokines and hormones by these cells or as an associated immunologic response. These syndromes can be categorized by common causative mechanisms: hormonal syndromes, autoimmune syndromes, and other syndromes of less clear cause. Recent advances in medical technology have allowed better understanding of these syndromes and the development of novel diagnostic and therapeutic tools. Increased awareness of paraneoplastic syndromes associated with lung cancer should lead to the earlier recognition and diagnosis of malignancies, thereby improving the overall prognosis of patients and alleviating associated comorbidities. Despite the recent advances in recognizing and treating paraneoplastic syndromes, many questions remain to be answered.Current opinion in pulmonary medicine 07/2011; 17(4):260-8. · 3.12 Impact Factor
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ABSTRACT: INTRODUCTION: Zoledronic acid (Z) is a bisphosphonate used in hypercalcaemia-related cancer, in complications for bone metastasis and in postmenopausal osteoporosis and it has been related to osteoradionecrosis, especially when associated with radiation to the head and neck structures. OBJECTIVES: To determine the radiosensitization capacity of zoledronic acid in the combined treatment with ionizing radiation (IR) by evaluating its genotoxic and cytotoxic capacities in non-tumoral cells. MATERIALS AND METHODS: The genotoxic effect of Z was studied by means of the micronucleus test in cytokinesis-blocked cells of human lymphocytes irradiated before and after a 2 Gy irradiation, while the cytotoxic effect was studied by a cell viability test in the PNT2 cell line before and after exposure to different X-ray doses (0-20 Gy) in four groups (Z alone, radiation alone, Z + IR and IR + Z). RESULTS: A dose-dependent and time-dependent cytotoxic effect of Z and IR on PNT2 cells in vitro (p > 0.001) was demonstrated. With the concentrations recommended for humans, the combined treatment had a more pronounced effect than individual treatments (p < 0.001). The effect was synergic (CI < 1), increasing the Z enhancement ratio (2.6) and sensitization factor (56 %); the effect of Z was always greater after IR exposure. In the genotoxic effect, only the administration of Z after irradiation (IR + Z) increased chromosome damage (p < 0.001) and the sensibilization factor (35.7 %). CONCLUSION: High concentrations of Z are toxic, but the concentrations recommended for clinical practice in humans give it the characteristics of a radiosensitization agent, whose effect is even greater when administered after IR.Clinical and Translational Oncology 07/2012; · 1.28 Impact Factor
- Journal of Orthopaedic Science 04/2014; · 0.96 Impact Factor