Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 52-year-old patient presented himself with weight loss and night sweats. Laboratory analyses revealed a high sedimentation rate, elevated immunoglobulines and anaemia with sludge phenomenon. Differential diagnoses included Multiple Myeloma and Lymphoma. Having a risk constellation for HIV infection and just having recovered from oral thrush also made this diagnosis possible. Urinary analysis and chest x-ray were normal; however, CT-scan detected renal cell cancer with pulmonary metastases. Renal cell cancer is heterogeneous in presentation, symptoms are unspecific, therefore they are often discovered late when they have already metastasized. Paraneoplastic syndromes, e.g. hypercalcaemia or hypertension are not infrequent in renal cell cancer.
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PMID:[Weight loss and night sweats with unexpected tumor localization]. 1807 82

Cases of patients developing lymphoma and cutaneous neoplasms after long-term methotrexate therapy are well documented in the literature; however, there are no reported cases of other neoplasms resulting from methotrexate therapy. A 52-year-old woman who had been on methotrexate for 9 years for psoriatic arthritis was found to have abnormal liver function tests on screening. Investigation with ultrasound, CT scanning and MRCP showed a hilar cholangiocarcinoma and a synchronous right renal tumour. A left hemi-hepatectomy extended to segments 5 and 8 with the formation of a hepaticojejunostomy was performed for a poorly differentiated infiltrative hilar cholangiocarcinoma. This was combined with a right radical nephrectomy for a T1 renal cell adenocarcinoma. Postoperative vomiting was subsequently found to be due to hypercalcaemia and primary hyperparathyroidism. A parathyroid adenoma was later excised. It seems likely that treatment with methotrexate was causal in the development of these three non-cutaneous neoplasms-two malignant and one benign.
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PMID:Cholangiocarcinoma, renal cell carcinoma and parathyroid adenoma found synchronously in a patient on long-term methotrexate. 1833 65

A 60-year-old Japanese man presented to our hospital with a painful left hip. Computed tomography showed a tumor in the left kidney and metastases in the left gluteus maximus muscle and lung. The pathological diagnosis of a biopsy specimen obtained from a metastatic lesion in the left gluteus maximus muscle was sarcomatoid renal cell carcinoma. On admission, his general condition was extremely poor. He was confined to bed because of severe left hip pain and confusion, possibly caused by hypercalcemia. This seriously ill patient suffering from advanced sarcomatoid renal cell carcinoma was treated with single-agent gemcitabine, resulting in symptom relief and a dramatic improvement in his status; all of the tumors had regressed significantly by the 11th dose of gemcitabine. These findings indicate that single-agent gemcitabine is one of the few chemotherapeutic agents effective for palliation in patients with sarcomatoid renal cell carcinoma, even those with poor performance status.
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PMID:Remarkable shrinkage of sarcomatoid renal cell carcinoma with single-agent gemcitabine. 1845 54

Bisphosphonates represent nowadays a standard therapy of tumor induced hypercalcemia and are progressively more used in the treatment of tumor bone metastatic disease. Among several bisphosphonates, pamidronate is one of the most commonly used in clinical practice, so we also used it in succesful treatment of patients with breast cancer bone metastases. It has been shown that pamidronate reduces the frequency of hypercalcemia, bone pain and pathological fractures, although the mechanisms by which these effects are achieved are not completely clarified. Bisphosphonates are also important not only in treating patients with present metastases but also in prevention, or at least, delay of bone metastases onset. Recently, there are clinical trials examining the so called adjuvant therapy, that means the use of bisphosphonates in prevention of bone metastases in high risk breast cancer patients without distant metastases. In addition to breast cancer, multiple myeloma is another area of successful bisphosphonate application. In this paper we present some of the clinical results following the use of pamidronate in breast cancer- and hypernephroma-patients with hypercalcemia.
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PMID:[Current use of bisphosphonates in clinical oncology]. 1965 72

Sunitinib is a novel oral multitargeted tyrosine kinase inhibitor. It has higher response rates and progression-free survival in patients with metastatic renal cell carcinoma (RCC) when compared with standard chemotherapy and interferon-alpha. We report a case of paraneoplastic hypercalcemia, resistant to conventional treatment but recovers by sunitinib treatment as the first case in the literature, in a 33-years-old man with metastatic RCC. At the sixth month of follow-up period, in this case, serum calcium level was still in normal ranges. Besides sunitinib is effective in symptom control, it is also helpful in management of paraneoplastic hypercalcemia, a life-threatening entity.
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PMID:Recovery of paraneoplastic hypercalcemia by sunitinib treatment for renal cell carcinoma: a case report and review of the literature. 1983 Jun 2

Bone is the second most common metastatic site in patients with renal cell carcinoma presenting with metastases (mRCC) at diagnosis. Complications of metastatic bone disease, including bone pain, fractures, spinal cord compression, and hypercalcaemia, are the primary cause of decline in the quality of life of patients with mRCC. Currently, treatment for mRCC bone metastases is generally palliative. Bisphosphonates are also used; however, the efficacy of bisphosphonates in conjunction with targeted agents is currently unknown. As growth factors play a critical role in the development of bone metastases, there is a biological rationale for the use of targeted agents to treat them. We report here the case of two patients with mRCC with surgically unresectable sacral bone metastases treated with sunitinib, who are still alive with long-term stabilization of metastases of 48 and 31 months. Results suggest targeted agents such as sunitinib may be an effective treatment for bone metastases.
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PMID:Efficacy of sunitinib in patients with renal cell carcinoma with bone metastases. 2118 6

It has been known for over 50 years that the amount of nuclear chromatin (DNA) in malignant neoplasms differs from that of homologous normal cells (1). More recently, it has been shown that nuclear DNA content correlates with the clinical outcome of various human neoplasms including urologic malignancies (2-10). An important problem in the care of patients with renal cell carcinoma (RCC) is the prediction of the neoplasms malignant potential, and in turn the patient's prognosis. Various parameters have been used to assess the malignant potential of renal cell carcinoma, including clinical and pathologic stage, histologic grade, tumor size, nuclear morphology, immunohistochemistry, age, elevated erythrocyte sedimentation rate, and hypercalcemia. To date, the most important predictors of prognosis in patients with RCC have been tumor pathologic stage, histologic grade and type (11,12). However, it has been shown that patients within a specified stage and grade may differ in their disease progression and survival (13,14). Furthermore, none of these variables alone or in combination has shown to provide total reliable prognostic information for the individual patient. These reasons led several groups to evaluate the prognostic value of nuclear DNA content in patients with renal cell carcinoma.
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PMID:Static and flow cytometry. 2131 9

Renal cell cancer (RCC) has an increasing incidence internationally and is a disease for which there have been limited therapeutic options until recently. The last decade has seen a vastly improved understanding of the biological and clinical factors that predict the outcome of this disease. We now understand some of the different molecular underpinnings of renal clear cell carcinoma by mutation or silencing of the von Hippel Lindau (VHL) gene and subsequent deregulated proliferation and angiogenesis. Survival in advanced disease is predicted by factors (performance status, anemia, hypercalcemia, and serum lactate dehydrogenase, time from diagnosis to recurrence) incorporated into the Memorial Sloan Kettering Cancer Center (MSKCC) criteria (also referred to as 'Motzer' criteria). These criteria allow classification of patients with RCC into good, intermediate and poor risk categories with median overall survivals of 22 months, 12 months and 5.4 months, respectively. Predicated upon these advances, six new targeted drugs (sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab and pazopanib) have been tested in well-designed phase III trials, selected or stratified for MSKCC risk criteria, with positive results. All of these new drugs act at least in part through vascular endothelial growth factor (VEGF) mediated pathways with other potential therapeutic impact on platelet-derived growth factor (PDGF), raf kinase and mammalian target of rapamycin (mTOR) pathways. Importantly, data from each of these trials show a consistent doubling of progression-free survival (PFS) over prior standard of care treatments. In addition, sorafenib, sunitinib and temsirolimus, have demonstrated significant overall survival (OS) benefits as well; further follow-up is required to determine whether the disease control exhibited by everolimus and pazopanib will translate into a survival advantage. These drugs are generally well tolerated, as demonstrated by quality-of-life improvement in clinical trials, and result in clinical benefit for in excess of 70% of patients treated. They have challenged the traditional outcomes of clinical trial design by achieving their benefits with relatively few radiographic responses, but high rates of disease stability. The unique side-effect profile coupled with the chronicity of therapy requires increased vigilance to maximize exposure to the drugs while maintaining quality of life and minimizing toxicity. This review focuses on the background, clinical development and practical use of these new drugs in RCC.
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PMID:Targeted therapy in renal cancer. 2178 21

Bisphosphonates reduce the risk of skeletal-related events (SREs; i.e. spinal cord compression, pathological fracture, radiation or surgery to the bone, and hypercalcaemia) in patients with metastatic cancer. A number of analyses have been conducted to assess the cost effectiveness of bisphosphonates in patients with bone metastases secondary to breast cancer, but few in other solid tumours. This is a review of cost-effectiveness analyses in patients with non-breast solid tumours and bone metastases. A literature search was conducted to identify cost-effectiveness analyses reporting the cost per QALY gained of bisphosphonates in patients with metastatic bone disease secondary to non-breast solid tumours. Four analyses met inclusion criteria. These included two in prostate cancer (one of which used a global perspective but expressed results in $US, and the other reported from a multiple country perspective: France, Germany, Portugal and the Netherlands). The remaining analyses were in lung cancer (in the UK, France, Germany, Portugal and the Netherlands), and renal cell carcinoma (in the UK, France and Germany). In each analysis, the cost effectiveness of zoledronic acid versus placebo was analysed. Zoledronic acid was found to be cost effective in all European countries across all three indications but not in the sole global prostate cancer analysis. Across countries and indications, assumptions regarding patient survival, drug cost and baseline utility (i.e. patient utility with metastatic disease but without an SRE) were the most robust drivers of modelled estimates. Assumptions of SRE-related costs were most often the second strongest cost driver. Further review indicated that particular attention should be paid to the inclusion or exclusion of nonsignificant survival benefits, whether health state utilities were elicited from community or patient samples or author assumptions, delineation between symptomatic and asymptomatic SREs, and the methods with which SRE disutility was modelled over time. While the field of cost-effectiveness analysis in solid tumours other than breast cancer is still evolving, outcomes will likely continue to be driven by drug cost and assumptions regarding treatment benefits. Although considerations such as adverse events and administration costs are important, they were not found to influence cost-effectiveness estimates greatly. As zoledronic acid will lose patent protection in 2013 and subsequently be greatly reduced in price, it is likely that the field of cost effectiveness will change with regard to SRE-limiting agents. Meanwhile, research should be conducted to improve our understanding of the impact on quality of life and medical costs of preventing SREs.
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PMID:Pharmacoeconomics of bisphosphonates for skeletal-related event prevention in metastatic non-breast solid tumours. 2250 Sep 86

Most anticancer drugs entering clinical trials fail to achieve approval from the U.S. Food and Drug Administration. Drug development is hampered by the lack of preclinical models with therapeutic predictive value. Herein, we report the development and validation of a tumorgraft model of renal cell carcinoma (RCC) and its application to the evaluation of an experimental drug. Tumor samples from 94 patients were implanted in the kidneys of mice without additives or disaggregation. Tumors from 35 of these patients formed tumorgrafts, and 16 stable lines were established. Samples from metastatic sites engrafted at higher frequency than those from primary tumors, and stable engraftment of primary tumors in mice correlated with decreased patient survival. Tumorgrafts retained the histology, gene expression, DNA copy number alterations, and more than 90% of the protein-coding gene mutations of the corresponding tumors. As determined by the induction of hypercalcemia in tumorgraft-bearing mice, tumorgrafts retained the ability to induce paraneoplastic syndromes. In studies simulating drug exposures in patients, RCC tumorgraft growth was inhibited by sunitinib and sirolimus (the active metabolite of temsirolimus in humans), but not by erlotinib, which was used as a control. Dovitinib, a drug in clinical development, showed greater activity than sunitinib and sirolimus. The routine incorporation of models recapitulating the molecular genetics and drug sensitivities of human tumors into preclinical programs has the potential to improve oncology drug development.
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PMID:A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma. 2267 53


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