Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four intravenous regimens of pamidronate (Aredia) were evaluated for palliative treatment of bone metastases in 2 randomized open-label trials in patients with breast cancer (n = 61) or prostate cancer (n = 58). In breast cancer patients, administration of pamidronate 60 mg every 4 weeks, 60 mg every 2 weeks, or 90 mg every 4 weeks for 3 months resulted in statistically and clinically significant reductions in bone pain, with accompanying decreases in biochemical markers of bone turnover; a regimen of 30 mg every 2 weeks was not effective. Healing of bone lesions was observed in 25% of breast cancer patients. In prostate cancer patients, the same regimens of pamidronate produced reductions in bone pain, but no dose-response relationship was apparent. Moreover, there were no consistent changes in biochemical indices in these patients, and no healing of bone lesions occurred. The different response to pamidronate in those 2 patient populations may reflect the different severity of metastatic disease at baseline. Side effects of pamidronate were mild and transient in both studies.
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PMID:Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer. 753 91

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

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.
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PMID:In situ detection of parathyroid hormone-related protein in ovarian clear cell carcinoma. 904 5

Bone is one of the most frequent organs to be affected by metastatic cancer and causes more morbidity than any other metastatic site. Bisphosphonate treatment provides an organ-specific treatment which is relevant to most if not all tumour types involving bone. Bisphosphonates, particularly the potent agent pamidronate (Aredia), will relieve metastatic bone pain with a consequent improvement in quality of life in approximately 50% of patients. Long-term bisphosphonate treatment clearly reduces skeletal morbidity rates in multiple myeloma and breast cancer.
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PMID:How can we improve the treatment of bone metastases further? 980 53

Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.
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PMID:Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. 1137 39

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.
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PMID:[Use of disodium pamidronate in patients with bone metastases in patients with pulmonary carcinoma]. 1192 88

The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are significantly more effective than the selective estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen receptor-positive early breast cancer. Aromatase inhibitors are likely to replace SERMs as first-line adjuvant therapy for many patients. However, AIs are associated with significantly more osteoporotic fractures and greater bone mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing postmenopausal osteoporosis, cancer treatment-related bone loss, or skeletal complications of metastatic disease. Clinical practice guidelines recommend baseline and annual follow-up bone density monitoring for all patients initiating AI therapy. Bisphosphonate therapy should be prescribed for patients with osteoporosis (T score < -2.5) and considered on an individual basis for those with osteopenia (T score < -1). Modifiable lifestyle behaviors including adequate calcium and vitamin D intake, weight-bearing exercise, and smoking cessation should be addressed. Adverse events associated with bisphosphonates include gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These safety concerns should be balanced with the potential of bisphosphonates to minimize or prevent the debilitating effects of AI-associated bone loss in patients with early, hormone receptor-positive breast cancer.
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PMID:Aromatase inhibitors and bone loss. 1698 48

Background. The aim of this study was to evaluate the effectivness of connected therapy using strontium 89 or Sm153 (osteoblastic component) and bisphosphonate therapy (osteolytic component) in the group of breast cancer patients with multiple osteoblastic-osteolytic (mixt) bone metastases. <br /> Material and methods. The study included 16 patients with breast cancer and multiple bone painful metastases detected by scintigraphy and by radiogram or CT or MRI (the type of metastases). Each patient received a standard dose of strontium 89 (Metastron) or samarium 153 (Quadramet) combined with intravenous infusion of pamidronate (Aredia) or zoledronate (Zometa). The bisphosphonate therapy was repeated every month. For assessment of therapy effectivness; pain relief (VAS scale), a reduction in analgesic requirements and motor activity (ECOG and Karnofsky scale) were evaluated. The group of 10 patients treated with bisphosphonate only in the same time was observed. <br /> Results. We conclude that connected palliative therapy using strontium 89 and bisphosphonates is effective (66-75% "good" and "moderate" response rate) and safe for bone pain palliation in patients with multiple osteoblastic-osteolytic bone metastases from breast cancer. We have observed that the analgesic requirments decreased to 30% of dose on average. The motor activity of the points evaluated according to ECOG scale increased from 3 to 2 and from 50 to 60 to Karnofsky scale. <br /> Conclusions. The results of treatment in the group with radioisotope and bisphosphonate were better than in the group treated with bisphosphonates or radioisotope only.
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PMID:Preliminary results of combined application of radioisotopes and biphosphonates in the management of pain associated with osteoblastic-osteolytic bone metastases of breast cancer. 1803 12

Bisphosphonates (BPs), as inhibitors of osteoclasts, are widely used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. Recent cases of bone necrosis of the jaws have been associated with the use of bisphosphonate therapy. A case is presented of a patient with osteonecrosis of the maxilla with a history of long-term bisphosphonate therapy for metastatic breast cancer. The authors treated the patient and suggest appropriate patient management guidelines with reference to current knowledge. Although a definitive treatment for bisphosphonate-associated osteonecrosis has not yet been established, clinicians must be aware of the pharmacologic properties of several bisphosphonates currently available and their indications, susceptible risk factors in the development of osteonecrosis of the jaws, the clinical signs and symptoms, and recommendations for patient management, including prevention and early recognition. BPs, potent inhibitors of osteoclast-mediated bone resorption, were first introduced more than 20 years ago. Since then, they have been used widely in the management of bone diseases, including hypercalcemia related to malignancy, myeloma-related bone disease, Paget's disease and osteoporosis. They have also been shown to inhibit tumor cell proliferation and inhibit angiogenesis. These additional features have made BPs useful in the treatment of metastatic disease, including breast and prostate cancer, resulting in a rise in the medical use of these drugs. However, recent reports suggest that BPs, particularly the nitrogen-containing BPs pamidronate (Aredia) and zoledronic acid (Zometa), both manufactured by Novartis of East Hanover, NJ, are capable of causing bisphosphonate-associated osteonecrosis of the jaw (BON). With 2.5 million patients treated with pamidronate and/or zoledronate worldwide, BON occurs in about one per 10,000 treated patients (Novartis, unpublished data, 2004). Currently, the total number of reported cases associated with alendronate (Fosamax, Merck and Co. Inc., White-house Station, NJ) the most commonly prescribed oral bisphosphonate, is approximately 170 worldwide (C. Arsver, oral communication, March 2006). This corresponds to a spontaneous BON incidence of approximately 0.7 cases per 100,000-years exposure. However, there is insufficient data to determine why the osteonecrosis reported seems to particularly affect the jaw, with a slightly higher rate in the mandible than the maxilla. This report concerns the management of a patient with BON. Information provided includes: the pharmacologic properties of the several bisphosphonates currently available; the pathobiological mechanism; the clinical presentation of the oral lesions; and recommendations for the oral management of patients who have received BP therapy, with consideration of a preventative approach based on current knowledge.
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PMID:Bisphosphonate-associated osteonecrosis: a clinician's reference to patient management. 1876 52

The infamous "phossy jaw" that created an epidemic of exposed bone osteonecrosis exclusively in the jaws began around 1858 and continued until 1906, with only a few cases appearing since that time. This epidemic of osteonecrosis produced pain, swelling, debilitation, and a reported mortality of 20% and was linked to "yellow phosphorous," the key ingredient in "strike-anywhere" matches. In match-making factories, workers called "mixers," "dippers," and "boxers" were exposed to heated fumes containing this compound. Related to the duration of exposure, many of these workers developed painful exposed bone in the mouth, whereas their office-based counterparts did not. The exposed bone and clinical course were eerily similar to what modern day oral and maxillofacial surgeons see due to bisphosphonates used to treat metastatic cancer deposits in bone or osteoporosis. Although yellow phosphorus has a simple chemistry of P(4)O(10), when combined with H(2)O and CO(2) from respiration and with common amino acids, such as lysine, bisphosphonates almost identical to alendronate (Fosamax; Novartis Pharmaceuticals, East Hanover, NJ) and pamidronate (Aredia; Novartis Pharmaceuticals) result. Forensic evidence directly points to conversion of the yellow phosphorus in patients with "phossy jaw" to potent amino bisphosphonates by natural chemical reactions in the human body. Thus, the cause of phossy jaw in the late 1800s was actually bisphosphonate-induced osteonecrosis of the jaws, long before clever modern pharmaceutical chemists synthesized bisphosphonates. Today's bisphosphonate-induced osteonecrosis represents the second epidemic of "phossy jaw." Case closed.
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PMID:Uncovering the cause of "phossy jaw" Circa 1858 to 1906: oral and maxillofacial surgery closed case files-case closed. 1894 May 6


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