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

In view of previous animal studies showing that pamidronate (Aredia) can cause renal damage, and human data indicating that pamidronate in doses of 60-90 mg is more effective in the control of tumor-induced hypercalcemia than when given at lower doses, we decided to investigate whether pamidronate 90 mg infused over 60 minutes at weekly intervals had any adverse effects on renal function in patients with bone metastases. Twelve patients, 7 female (all with breast cancer) and 5 male (4 with prostate cancer, 1 with bladder cancer) were entered into the trial. Each patient received weekly intravenous infusions of pamidronate 90 mg in 250 ml normal saline over 60 minutes for 4 weeks. 51Cr-EDTA clearances showed no significant changes in renal function. Urinary N-acetyl-B-D-glucosaminidase/creatinine ratios fluctuated considerably, but no consistent changes were found. No patient with a normal level of urinary beta 2-microglobulin had elevated levels at the end of the trial. Serum creatinine levels did not change significantly, though 1 patient had a corrected serum calcium level of < 2 mmol/L on a single occasion on day 8. No evidence of renal toxicity was detected. However, the possibility that neprohtoxicity would ultimately appear cannot be excluded, and these favourable short-term results cannot be extrapolated to patients with impaired renal function.
 ...
PMID:Intravenous pamidronate: infusion rate and safety. 787 59

A total of 295 patients with lytic bone metastases from breast cancer were randomized to receive chemotherapy or chemotherapy plus pamidronate (Aredia) 45 mg intravenously every 3 weeks. Primary endpoints were time to progressive bone disease (evaluated by blind extramural review), and improvement in pain (according to a 6-point self-assessment scale). Secondary endpoints included incidence of bone-related complications (pathological fractures, tumor-induced hypercalcemia, need for radiotherapy), sclerotic response of lytic lesions, WHO performance status, and analgesic score. Median time to bone progression was 249 days and 168 days in the pamidronate and control groups respectively (p = 0.02). Marked improvement in bone pain was observed in 44% of patients receiving pamidronate compared to 30% in controls (p = 0.025). With respect to secondary endpoints, pamidronate reduced the need for radiotherapy (66 times vs. 82 times in controls), and median time to radiotherapy was 697 days with pamidronate, 571 in the control arm. No severe adverse reactions or worsening of chemotherapy-induced toxicities were observed during 1598 pamidronate infusions. We conclude that intravenous pamidronate is well tolerated, significantly prolongs time to progressive bone disease, and significantly improves bone pain in patients with osteolytic metastases from breast cancer.
 ...
PMID:Delayed progression of bone metastases with pamidronate therapy in breast cancer patients: a randomized, multicenter phase III trial. 787 61

Frequent complications of bone metastases include pain, pathologic fracture, hypercalcemia and spinal cord compression. Lytic bone metastases result from excessive activation of osteoclasts by tumor-produced cytokines. Aredia (pamidronate) is a potent bisphosphonate that inhibits osteoclast activation. In two dose-seeking phase I trials in patients with breast cancer and prostate cancer, repeated intravenous infusion of Aredia was shown to be safe and effective in reducing bone resorption and pain. In a randomized phase III trial of 377 patients with multiple myeloma, Aredia was administered in a dosage of 90 mg i.v. every 4 weeks. Compared with placebo, treatment with Aredia was associated with a significant decrease in bone pain and in the incidence and time to development of all skeleton-related events. Data from two phase III breast cancer trials each involving 300 patients are now being analyzed. The newer bisphosphonates can safely be used together with standard anticancer therapy to provide effective palliation of symptoms caused by lytic bone metastases.
 ...
PMID:The role of bisphosphonates in the treatment of bone metastases--the U.S. experience. 873 55

A case of ovarian clear cell carcinoma associated with hypercalcemia is reported. A 67-year-old woman developed the lung metastasis 8 months after primary surgery. The patient manifested symptoms of humoral hypercalcemia of malignancy (HHM) during the last 3 months of her clinical course. Serum and urinary C-terminus parathyroid hormone-related protein (PTHrP) levels were remarkably high. No increase in interleukin (IL) 1beta, tumor necrosis factor (TNF) alpha, vitamin D3 metabolites or intact PTH was detected. Pamidronate disodium treatment was transiently suppressed her serum calcium level. The patient died despite seven courses of chemotherapy. Autopsy showed multiorgan metastases and accelerated osteoclastic bone resorption; skeletal metastasis was not detected. Immunohistochemical analysis clearly showed the localization of PTHrP at both the primary and metastatic sites. The transcripts of PTHrP at pulmonary metastatic sites were revealed by in situ hybridization and the reverse transcription polymerase chain reaction (RT-PCR) method. PTHrP was the causative factor for HHM in this case. It is therefore suggested that hypercalcemia may have occurred after PTHrP production had overcome the homeostatic level during the terminal stage, although PTHrP production continued irrespective of the patient's serum calcium level.
 ...
PMID:In situ detection of parathyroid hormone-related protein in ovarian clear cell carcinoma. 904 5

The authors describe the case of a 20-year-old patient where the first leading symptom was hypercalcaemia. A similar case was not published so far in the Czech literature. The disease took a fulminant course and proved fatal nine days after the first symptoms of the disease. The correct diagnosis was established only by necropsy. The adverse course of the disease could not be influenced by repeated haemodialysis nor by the administration of disodium pamidronate (Aredia) and calcitonin. The authors discuss differential diagnostic problems of hypercalcaemias and the pathogenesis of hypercalcaemia in malignant diseases of the haematopoietic system.
 ...
PMID:[Hypercalcemia as the first manifestation of bone marrow T-cell lymphoma]. 922 Nov 99

A total of 91 breast cancer patients died of advanced and recurrent breast cancer at the Osaka Teishin Hospital from 1986 to 1996. There were 18 cases (19.8%) among them showing hypercalcemia (serum corrected Ca > or = 11.0 mg/dl). These 18 cases were analyzed to determine the incidence of hypercalcemia and to find a more effective treatment. All these patients had multiple bone metastases during their clinical course, and six patients (33.3%) had pathologic bone fracture just before the occurrence of hypercalcemia. Their common symptoms were general fatigue, gastrointestinal symptoms, renal dysfunction or neurological symptoms. There was no definitive correlation between clinical signs and serum calcium values. Among various therapies, the use of pamidronate disodium (Aredia) in combination with hydration, steroid and calcitonin was found to be the most effective treatment for hypercalcemia. The survival time from the diagnosis of hypercalcemia in the patients undergoing treatment with Aredia was significantly better than without it (p < 0.01). This suggests that Aredia should be effective and useful for advanced breast cancer patients with hypercalcemia.
 ...
PMID:[Analysis of 18 breast cancer patients with hypercalcemia]. 961 23

Prolonged immobilization or physical inactivity has been shown to produce increased bone resorption due to enhanced osteoclastic activity and diminished bone formation. These skeletal changes are a typical complication in tetraplegic patients, who are at risk of developing hypocalcemia. Hypercalciuria is the most characteristic symptom. However, some patients develop hypercalcemia, which is infrequent in these patients, and the hypercalcemia can become a life-threatening complication. Until now, it has been unclear why a small percentage of immobilized patients develop hypercalcemia. Here we present a case of symptomatic hypercalcemia (serum calcium: 3.5 mM/l) following immobilization due to a critical illness polyneuropathy. The diagnosis could be established after malignant hypercalcemia, primary hyperparathyroidism, and other causes of hypercalcemia were excluded. Treatment with intravenous saline, furosemide, and calcitonin was not effective in lowering serum calcium. Treatment with pamidronate (Aredia) was successful and reduced the serum calcium to normal values.
 ...
PMID:[Immobilization hypercalcemia as a complication of polyneuropathy]. 1099 16

Metastatic bone disease develops as a result of the many interactions between tumour cells and bone cells. This leads to disruption of normal bone metabolism, with the increased osteoclast activity seen in most, if not all, tumor types providing a rational target for treatment. The clinical course of metastatic bone disease in multiple myeloma, breast and prostate cancers is relatively long, with patients experiencing sequential skeletal complications over a period of several years. These include bone pain, fractures, hypercalcaemia, and spinal cord compression, all of which may profoundly impair a patient's quality of life. External beam radiotherapy and systemic endocrine and cytotoxic treatments are the mainstay of treatment in advanced cancers. However, it is now clear that the bisphosphonates provide an additional treatment strategy, which reduces both the symptoms and complications of bone involvement. Pamidronate (Aredia(TM)) is the most widely evaluated bisphosphonate and is recommended for most patients with multiple myeloma or breast cancer with bone metastases. Current research aims include the evaluation of new potent bisphosphonates such as zoledronic acid (Zometa(TM)). It is hoped that this compound is not only more convenient and easier to administer but also more effective in inhibiting skeletal morbidity. Zometa may also have some direct anticancer activity. Preclinical studies with Zometa have demonstrated its potential in malignant bone disease. Clinical studies in treatment of hypercalcemia of malignancy have been completed, as have Phase I and II trials in patients with cancer and pre-existing bone metastases. Three randomized, double-blind, controlled Phase III trials are now ongoing to establish the efficacy and safety of Zometa in treatment of bone metastases in patients with osteolytic and osteoblastic lesions. Additionally, new specific molecules such as osteoprotogerin have been developed that are based on our improved understanding of the cellular signalling mechanisms involved in cancer induced bone disease. These potent molecules are now entering clinical trials. Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate in metastatic bone disease and their use in the prevention and treatment of osteoporosis in cancer patients. In vitro suggestions of direct anti-cancer activity and some promising clinical data in early breast cancer have resulted in considerable interest in the possible adjuvant use of bisphosphonates to inhibit the development of bone metastases.
 ...
PMID:Optimising treatment of bone metastases by Aredia(TM) and Zometa(TM). 1111 66

Disodium pamidronate (Aredia), a drug of the bisphosphonate group, was administered to 20 patients with pains in the bones due to secondary deposits of lung cancer. The aim of the study was to investigate the analgesic effect of pamidronate to osteolytic metastases of lung cancer in the bone. In 16 (80%) patients non-small-cell lung cancer was diagnosed, and in 4 (20%) patients small-cell-lung cancer was confirmed. Intensive disseminated pains in the bones were present in all the patients. Metastases in the skeleton were confirmed by radiography and scintigraphy of the bones. Initial values of calcium in the plasma were determined in those patients. In 11 (55%) patients, initial values of calcium in the serum were normal, and in 9 (45%) patients, they were elevated. Patients with normal calcium values received 30 mg of pamidronate in 250 ml of normal saline, and patients with hypercalcemia received 45-60 mg in 500 ml of normal saline. Analgesic effect of pamidronate was present in 12 (60%) patients, and the completely painless state was achieved in 4 out of 12 patients. Evaluation of the pain was done by questionnaire, using a simple, descriptive scale. In all 9 (100%) patients with hypercalcemia, values of calcium in plasma were normalized. Pamidronate exerted favorable analgesic effect in the case of metastases of lung cancer in the bones in more than 50% patients. Satisfactory results were also achieved in the patients non-responsive to palliative therapy by irradiation. This enables the use of opiates in lower doses.
 ...
PMID:[Use of disodium pamidronate in patients with bone metastases in patients with pulmonary carcinoma]. 1192 88

Less than 25 years ago, tumor-induced hypercalcemia was often a lethal complication of cancer. Nowadays, it can be successfully and easily treated in at least 90% of the cases by rehydration and potent antiosteoclastic bisphosphonates. The standard therapy consists of the administration of 90 mg of pamidronate (Aredia Dry Powder) or more recently, 4 mg of zoledronic acid (Zometa)], which is even more efficient, at least in patients without bone metastases. Recurrent hypercalcemia is nevertheless difficult to control and antibodies against parathyroid-hormone-related protein may prove to be a useful treatment.
 ...
PMID:Treatment of tumor-induced hypercalcemia: a solved problem? 1272 83


1 2 Next >>