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.
"Currently, the only kinds of therapies that can treat bone metastases are supportive therapies using 1) bisphosphonates to reduce osteolytic burden, 2) radiotherapy and analgesics to alleviate pain, and 3) surgical intervention to reinforce weak bones.24,118,119 The humanized monoclonal antibody to the IL-6 receptor, tocilizumab (Actemra®) was approved by the United States Food and Drug Administration (FDA) on January 11, 2010 and was previously approved in Japan and the European Medicines Agency (EMEA) in 2008 (Table 1).120 "
[Show abstract][Hide abstract] ABSTRACT: Metastatic events to the bone occur frequently in numerous cancer types such as breast, prostate, lung, and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma. Accumulating evidence suggests that the inflammatory cytokine interleukin (IL)-6 is frequently upregulated and is implicated in the ability of cancer cells to metastasize to bone. IL-6 is able to activate various cell signaling cascades that include the STAT (signal transducer and activator of transcription) pathway, the PI3K (phosphatidylinositol-3 kinase) pathway, and the MAPK (mitogen-activated protein kinase) pathway. Activation of these pathways may explain the ability of IL-6 to mediate various aspects of normal and pathogenic bone remodeling, inflammation, cell survival, proliferation, and pro-tumorigenic effects. This review article will discuss the role of IL-6: 1) in bone metabolism, 2) in cancer metastasis to bone, 3) in cancer prognosis, and 4) as potential therapies for metastatic bone cancer.
Cancer Management and Research 05/2011; 3(21625400):177-89. DOI:10.2147/CMR.S18101
[Show abstract][Hide abstract] ABSTRACT: Bisphosphonates (BPs) are widely used in the management of metastatic bone disease to reduce skeletal morbidity. Zoledronic acid (ZA), the most potent BP in clinical use, has demonstrated clinical utility in multiple tumour types. Preclinical data indicate that ZA may have direct antitumour activity, as has been demonstrated preclinically in both in vitro and in vivo experiments. The majority of preclinical studies showing antitumour effects have used high doses of ZA, making it difficult to translate these data to the clinical setting. This review summarises the published data on antitumour effects of ZA in tumour cell lines, mice experiments, and human clinical trials. Translational questions regarding drug dose, dose interval, and sequence with chemotherapy treatment are also addressed.
[Show abstract][Hide abstract] 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. DOI:10.1097/MCP.0b013e328347bdba · 2.76 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.