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 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.
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PMID:Delayed progression of bone metastases with pamidronate therapy in breast cancer patients: a randomized, multicenter phase III trial. 787 61

In a retrospective study survival after hypercalcemia in breast cancer patients has been investigated. A group of 72 patients were treated with bisphosphonate APD [3-(amino-1,1-hydroxypropylidene)bisphosphonate] and third-generation amino-containing bisphosphonates between January 1980 and October 1992. A median survival of 4.5 months was found. In a multivariate analysis, four independent prognostic factors for survival have been found: the interval between first relapse and hypercalcemia, sites of metastases at the moment of hypercalcemia, primary treatment, and the level of serum alkaline phosphatase. Patients with a "flare" reaction on tamoxifen treatment and patients with a normal serum alkaline phosphatase level and bone metastases only had a prolonged survival. Hypercalcemia associated with visceral metastases carried a very poor prognosis. The level of serum calcium in this series of patients was no prognostic indicator for survival.
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PMID:Hypercalcemia in patients with breast cancer: a survival study. 792 33

The established pre-operative therapy for severe hypercalcemia caused by primary hyperparathyroidism (pHPT), i.e., rehydration with saline in combination with furosemide, calcitonin and hydrocortisone, rarely leads to satisfactory results. We examined the effect of pamidronate (APD, 45-60 mg), a diphosphonate of the 2nd generation in 6 patients (4 female, 2 male) with severe hypercalcemia caused by pHPT. Prior administration of saline, furosemide, calcitonin and oral diphosphonates of the 1st and 2nd generation had failed and the patients still suffered from symptoms of hypercalcemia. APD reduced serum calcium levels in all patients: values reached the normal range (2.1-2.6 mmol/l) in 3 patients, the upper normal range in 2 patients and fell transiently into the subnormal range in 1 patient. In parallel to the decreasing calcium levels a marked increase in PTH was registered in 4 out of 6 patients. One patient with an adenoma showed no change in PTH levels, whereas one patient with hyperplasia of 5 parathyroid glands showed a significant decrease in PTH. These results confirm the potent hypocalcemic effect of pamidronate even in patients whose serum calcium could not be reduced by other conservative therapeutic strategies. Thus, pamidronate is an effective drug in the treatment of the pre-operative phase of hypercalcemia caused by pHPT.
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PMID:[Disodium pamidronate (APD) in therapy of hypercalcemia in primary hyperparathyroidism]. 809 66

Pamidronate (APD) is a drug widely used for the treatment of hypercalcemia of malignancy. Renal impairment has been associated with the use of other bisphosphonates in humans, and nephrotoxicity has been described after APD administration in animals. We retrospectively evaluated the safety and efficacy of APD administration in 31 patients with underlying renal insufficiency who received 33 courses of APD in doses of 60-90 mg. Hypercalcemia resolved or improved in 91% of the patients and only 1 case had severe hypocalcemia. A transient deterioration in renal function was observed in 8 courses but this was unrelated to APD administration. No systemic ill effects were observed. APD appears to be a safe drug in patients with underlying renal failure.
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PMID:Safety of pamidronate in patients with renal failure and hypercalcemia. 870 58

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.
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PMID:The role of bisphosphonates in the treatment of bone metastases--the U.S. experience. 873 55

Oral pamidronate (APD) at high doses (400-900 mg/day) is employed as antiresorptive agent for the treatment of Paget's disease. In some occasions hypocalcemia may occur, and is interpreted as a relative overdosage. To avoid this complication and the consequent PTH release, supplementation with calcium salts is recommended. In osteoporotic syndromes, APD is prescribed at a lower dosage (200 mg/day) and currently calcium or vitamin D are also systematically added. But at this low dose the antiresorptive activity is partial and transient. In order to observe the effects on calcemia of multiple therapy, data from 129 postmenopausal women with the diagnosis of osteopenia or osteoporosis treated with 200 mg/day of APD soft capsules during 6-10 months, were gathered retrospectively. The first group (n: 13) received APD alone; the second group was supplemented with 1 g/day calcium salts (n: 61); the third group received 0.015-0.025 mg/day vitamina D (n: 10); and the fourth received both calcium plus vitamin D (n: 45). In samples of 24 h, urine, calcium, creatinine, hydroxyproline, and serum total calcium were measured before and after therapy. No hypocalcemia was detected. All groups, except the one treated with APD alone, showed a significant trend to increase their calcemia values between normal ranges (Table 1, 2). Only in one patient treated with APD + Ca + vitamin D, hypercalcemia was detected. Measuring HOP/Cr and Ca/Cr in urine as resorption markers, showed that 27% of the APD + Ca group and 33% of the APD + Ca + vitamin D group showed scant or any repercussion on mentioned resorption indexes, meaning that the response to APD could be hindered in those cases. In conclusion, while using low doses of oral APD, calcium salts should not be systematically recommended. There is no trend to hypocalcemia. Furthermore, calcium salts may favor drug interactions and so induce digestive side effects or poor responses. Calcium supplementation should be prescribed only on the basis of low calcium diet and not to prevent APD collateral effects on calcemia.
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PMID:[Effect of low doses of oral pamidronate (APD) on the calcemia of osteopenic or osteoporotic patients]. 893 64

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.
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PMID:[Hypercalcemia as the first manifestation of bone marrow T-cell lymphoma]. 922 Nov 99

Pamidronate (APD) is a potent inhibitor of bone resorption that is useful in the management of patients with osteolytic bone metastases from breast cancer or multiple myeloma, tumour-induced hypercalcaemia or Paget's disease of bone. After intravenous administration, the drug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix-bound pamidronate inhibits osteoclast activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cells to bone. In patients with osteolytic bone metastases associated with either breast cancer or multiple myeloma, administration of pamidronate together with systemic antitumour therapy reduces and delays skeletal events, including pathological fracture, hypercalcaemia and the requirement for radiation treatment or surgery to bone. Pamidronate generally improves pain control. Quality-of-life and performance status scores in pamidronate recipients were generally as good as, or better than, those in patients who did not receive the drug. Overall survival does not appear to be affected by pamidronate therapy. Tumour-induced hypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatment. Response durations vary, but are commonly 3 weeks or longer, In comparative studies, pamidronate produced higher rates of normocalcaemia and longer normocalcaemic durations than other available osteoclast inhibitors, including intravenous etidronate, clodronate and plicamycin (mithramycin). In most patients with Paget's disease of bone, intravenous pamidronate reduces bone pain and produces biochemical response. Serum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may be prolonged. Pamidronate is well tolerated by most patients. Transient febrile reactions, sometimes accompanied by myalgias and lymphopenia, occur commonly after the first infusion of pamidronate. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcaemia and, rarely, ocular complications (uveitis and scleritis). Pamidronate should be considered for routine use together with systemic hormonal or cytotoxic therapy in patients with breast cancer or multiple myeloma and osteolytic metastases. At present, pamidronate is the drug of choice for first-line use in the management of patients with tumour-induced hypercalcaemia. It is an effective treatment for Paget's disease and is the treatment of choice where oral bisphosphonates are not an option.
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PMID:Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget's disease of bone. 950 93

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.
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PMID:[Analysis of 18 breast cancer patients with hypercalcemia]. 961 23

Human hypercalcemia of malignancy (HHM) is generally due to the release into the circulation of parathyroid hormone-related peptide (PTHrP). PTHrP stimulates osteoclastic bone resorption and renal calcium reabsorption through the activation of a receptor similar to that of PTH (PTH-R). However, there is scarce information about the PTH-R regulation in the setting of the hypercalcemia. In the present study, we assessed the molecular basis of renal PTH-R regulation in Walker tumor-bearing rats either treated or not by a bisphosphonate, pamidronate. Twenty-seven 6-week-old rats were randomly divided into three experimental groups: WC- APD- (9 control rats), WC+ APD- (9 Walker tumor-bearing rats), and WC+ APD+ (9 Walker tumor-bearing rats receiving 15 mg/kg/day of sodium pamidronate every day for seven days). Pamidronate induced a significant decrease in the mean tumor weight (9.3+/-0.8 vs 6.3+/-0.6 g). Seven days after the subcutaneous implantation of the Walker cells, plasma total calcium was 10.8+/-0.4, 16.8+/-0.6, and 12.9+/-0.6 mg/dl in WC- APD-, WC+ APD-, and WC+ APD+, respectively. Plasma PTHrP concentration was undetectable, 15.9+/-2.6, and 7.2+/-1.4 pmol/l, respectively. Bone histomorphometric results showed high resorption in WC+ APD-, which returned below the basal level of the WC- APD- with pamidronate treatment. Densitometric analysis of Northern blots revealed that the renal PTH-R mRNA expression in WC+ WPD- rats was a quarter of the levels in the WC- APD- and WC+ APD+ groups. WC+ APD- also had a decreased PTH-stimulated cAMP production in renal membranes. The PTH-R was expressed in the Walker tumor and it was not modified by pamidronate treatment. In conclusion, the expression of PTH-R receptor mRNA is significantly reduced in the kidney of rats bearing Walker carcinoma tumor. Its regulation is tissue-specific: pamidronate, which partially corrected the hypercalcemia and elevated circulating PTHrP, normalized the PTH-R mRNA expression in the kidney but not in the tumor.
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PMID:Pamidronate corrects the down-regulation of the renal parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor mRNA in rats bearing Walker tumors. 966 83


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