Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zoledronic acid (Zometa) is the most recent addition to the clinically available bisphosphonates. Clinical benefits in metabolic, as well as cancer-related bone disease have been observed. In addition to its profound antiosteoclast effects, it has demonstrated anticancer effects in preclinical models. Zoledronic acid has been evaluated in randomized, double-blind clinical trials of osteoporosis, Paget's disease of bone, and metastatic, osteolytic and osteoblastic bone disease. Antiosteoclast activity has been demonstrated by reductions in the bone breakdown products N-telopeptide, C-telopeptide and deoxypyridinoline. Bone mineral density, measured by dual energy x-ray absorptometry, is increased with administration of zoledronic acid in postmenopausal osteoporosis. Clinical benefit in cancer includes improvement in bone pain, reductions in skeletal events and delay in time-to-first-skeletal-events. These zoledronic acid treatment benefits have been demonstrated in patients with multiple myeloma, breast, prostate and lung cancer, and other solid tumors.
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PMID:Zoledronic acid (Zometa) use in bone disease. 1272 75

Painful and life-threatening skeletal complications are common in patients with advanced cancer metastatic to bone. Patients with breast cancer and multiple myeloma who survive for 2 or more years after developing bone metastases/lesions are at chronic risk for skeletal complications. Patients with prostate cancer and other solid tumors are also at high risk for skeletal complications, and, until recently, no effective treatment had been identified. Zoledronic acid, a new-generation bisphosphonate, was recently shown to be safe and effective as treatment for the prevention of skeletal complications in three randomized, phase III trials involving more than 3000 patients with multiple myeloma, breast, prostate, and lung cancers, and other solid tumors. Zoledronic acid (4 mg) was at least as effective as pamidronate (90 mg) in preventing skeletal complications in the overall study population of patients with breast cancer and multiple myeloma and was superior to pamidronate in the subset of over 1000 patients with breast cancer. In patients with solid tumors, including prostate cancer and lung cancer, zoledronic acid significantly reduced the incidence and delayed the onset of skeletal complications compared with placebo. Zoledronic acid is the first bisphosphonate with broad clinical utility and may become the preferred bisphosphonate for the treatment of bone metastases in patients with advanced cancers.
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PMID:Zoledronic acid for the treatment of bone metastases in patients with breast cancer and other solid tumors. 1461 36

Many advanced cancers, particularly breast cancer and prostate cancer, metastasize to the bone, resulting in painful lesions and skeletal complications. Intravenous bisphosphonate therapy is an important component of palliative care for patients with bone metastases, and pamidronate has been the standard of care for patients with breast cancer and multiple myeloma since 1996. However, zoledronic acid is the first bisphosphonate shown to significantly reduce skeletal morbidity in patients with a wide range of primary tumor types. Zoledronic acid has demonstrated efficacy in the management of hypercalcemia and metastatic bone disease. In phase III studies involving more than 3000 patients with multiple myeloma, breast cancer, prostate cancer, lung cancer, and other cancers, 4 mg zoledronic acid demonstrated consistent efficacy across a range of clinical end-points, and was safe and well tolerated when infused over 15 min. Based on these studies, zoledronic acid appears to be active in patients with bone metastases irrespective of tumor type, and should be considered as the standard of care for the treatment of bone metastases.
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PMID:Proven efficacy of zoledronic acid in the treatment of bone metastases in patients with breast cancer and other malignancies. 1465 40

Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ), pamidronate (Aredia; Novartis Pharmaceuticals Corp.), clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to that of placebo in patients with breast cancer. Zoledronic acid is the only bisphosphonate that has been compared directly with pamidronate, and it was shown by multiple event analysis to be significantly more effective at reducing the risk of an SRE. In patients with prostate cancer, clodronate, etidronate (Didronel; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and pamidronate have demonstrated transient palliation of bone pain. However, zoledronic acid is the only bisphosphonate to demonstrate both significant and sustained pain reduction and a significantly lower incidence and longer time to onset of SREs compared with placebo. Zoledronic acid is also the only bisphosphonate to demonstrate efficacy in patients with bone metastases from a variety of other solid tumors, including lung cancer and renal cell carcinoma. In conclusion, bisphosphonates effectively reduce skeletal complications in patients with bone metastases from breast cancer, and zoledronic acid has demonstrated the broadest clinical activity in patients with a wide variety of tumor types.
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PMID:Bisphosphonates: clinical experience. 1545 26

The introduction of zoledronic acid, a new-generation bisphosphonate, has greatly extended the use of bisphosphonates in the treatment of patients with bone metastases. On the basis of results from three large, randomized, phase III clinical trials enrolling more than 3,000 patients, zoledronic acid (4 mg via 15-minute infusion) was approved in the United States for the treatment of patients with documented bone metastases from solid tumors in conjunction with standard antineoplastic therapy and patients with multiple myeloma. Zoledronic acid is also approved in Europe for the prevention of skeletal-related events in patients with advanced malignancies involving bone. Current treatment guidelines published by the American Society of Clinical Oncology recommend the use of intravenous bisphosphonates at first radiographic evidence of osteopenia in patients with multiple myeloma or osteolytic bone lesions in patients with breast cancer to significantly reduce the occurrence and delay the onset of skeletal complications. Zoledronic acid has also demonstrated efficacy in the treatment of bone metastases in patients with prostate cancer, lung cancer, and other solid tumors. Bisphosphonate therapy is generally well tolerated but can be associated with increases in serum creatinine. Therefore, monitoring renal function is required for all patients receiving bisphosphonate therapy. Serum creatinine should be monitored before each dose and treatment withheld until any serum creatinine elevations have resolved to baseline levels. Caution should be exercised when treating patients who are receiving other potentially nephrotoxic therapies. With these simple precautions, intravenous bisphosphonate therapy is safe for long-term use and provides durable treatment benefits.
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PMID:Recommendations for zoledronic acid treatment of patients with bone metastases. 1585 80

Bone metastases are major sequelae of non-small-cell lung cancer and are associated with poor survival, skeletal-related events (SREs), and economic burden. In recent phase III trials, zoledronic acid has demonstrated a potential to prevent or delay SREs, although this has not yet translated into a survival benefit. Zoledronic acid is the first and only bisphosphonate with proven efficacy in the treatment of bone metastases associated with a broad range of tumors, including lung cancer. We report herein a case study that highlights the clinical benefit of zoledronic acid in a patient with squamous cell carcinoma of the lung.
Clin Lung Cancer 2005 Mar
PMID:Role of zoledronic acid in the setting of bone metastases from non-small-cell lung cancer. 1584 84

Bone metastases are a major cause of cancer morbidity. Bone metastases are associated with pain, fractures, spinal cord compression, ineffective haematopoiesis, and hypocalcaemia of malignancy. The goals of treatment for bone metastases are to prevent disease-related skeletal complications, palliate pain, and maintain quality of life. Bisphosphonates are a standard part of supportive care for patients with bone metastases. Zoledronic acid, a nitrogen containing third generation bisphosphonate, is the most active and is the most thoroughly investigated bisphosphonate for metastatic bone disease. The efficacy and safety of zoledronic acid has been established in three pivotal prospective, randomized controlled trials involving more than 3000 subjects. The evidence is reviewed here with a focus on clinical relevance. Across a broad array of tumour types, zoledronic acid (4 mg intravenously over 15 min every 3-4 weeks) decreased the frequency of skeletal-related events, delayed the time to a first skeletal-related event, and reduced pain. Zoledronic acid is more effective than pamidronate in breast cancer and the only bisphosphonate proven effective for metastatic prostate cancer, lung cancer, renal cell carcinoma and other solid tumours.
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PMID:Zoledronic acid to prevent skeletal complications in cancer: corroborating the evidence. 1622 55

Solid tumors frequently metastasize to bone. This results in debilitating skeletal complications such as intractable bone pain, pathologic fractures, spinal cord compression, and hypercalcemia. Patients frequently require palliative radiation therapy or orthopedic surgery. Bisphosphonates have been shown to delay the incidence and decrease the frequency of skeletal-related events. Zoledronic acid is the only bisphosphonate that has provided benefits for patients with bone metastases secondary to a broad range of solid tumors. Among patients with metastatic breast or prostate cancer, zoledronic acid has demonstrated significant reductions in pain and skeletal morbidity compared with placebo. Zoledronic acid has also shown significant reductions in skeletal morbidity in patients with lung cancer or other solid tumors compared with placebo. Zoledronic acid is generally well tolerated. Flu-like symptoms which are manageable with standard treatment can occur. Renal monitoring is recommended, with dose reductions for patients with renal dysfunction. Osteonecrosis has been reported in patients receiving bisphosphonates and might be avoidable with appropriate dental care.
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PMID:Efficacy and safety of intravenous bisphosphonates in patients with bone metastases caused by metastatic breast cancer. 1768 49

Patients with metastatic bone disease are at risk for developing skeletal-related events that can negatively influence quality of life, contributing to loss of autonomy and functional capabilities. Bisphosphonates have become an important component in the treatment of patients with bone metastases as they delay the onset and reduce the risk of skeletal-related events and also palliate or control bone pain in multiple cancer types, thus preserving quality of life. Zoledronic acid has proven efficacy and safety in patients with bone lesions from breast cancer, prostate cancer, lung cancer, and other solid tumors, as well as in patients with multiple myeloma. Current data suggest that early treatment with zoledronic acid (before the onset of bone pain) may provide additional clinical benefits and also positive effects on survival in subsets of patients who have elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker of bone resorption. Studies have shown that in patients with breast cancer, prostate cancer, lung cancer, or other solid tumors, normalization of elevated levels of NTX was observed in the majority of patients who received zoledronic acid. Furthermore, normalization of NTX values correlated with extended survival.
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PMID:Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease. 1806 86

In this study we have investigated changes in circulating angiogenic factors after a single zoledronic acid intravenous infusion. Thirty consecutive patients who had histologically confirmed breast (n=20) and lung cancer (n=10) associated with confirmation of bone metastases were included in the study. Serum was also available from 10 healthy volunteers. Four mg of Zoledronic acid (Zometa, Novartis) was administered as a 15-min infusion in 100-ml normal saline on an outpatient basis. Venous blood for assessment of serum parameters was drawn just before the beginning of drug infusion and again at 7 and 28 days after the zoledronic acid infusion. Serum levels of VEGF and bFGF were assayed with ELISA kits. Serum VEGF and bFGF levels were not significantly different from healthy control groups (P>0.05). However, we found that serum VEGF levels in lung cancer patients were significantly higher than in patients with breast cancer and controls (P=0.009, and P=0.022, respectively). We found no significant correlation between serum VEGF and bFGF levels. No statistically significant changes were seen following infusion of zoledronic acid in patients with bone metastases for both serum VEGF and bFGF levels (P>0.05). Unlike previous studies, zoledronic acid did not appear to exert an angiogenic activity as there was no reduction of VEGF and bFGF circulating levels after zoledronic acid infusion.
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PMID:Effect of zoledronic acid on serum angiogenic factors in patients with bone metastases. 1820 21


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