Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of long-term bisphosphonate (APD) treatment on the morbidity from bone metastases in breast cancer patients was studied in a controlled clinical trial. 131 patients were randomized between treatment with APD (300 mg/day orally) or control. Systemic treatment for breast cancer was left to the discretion of the physician. The distribution of cases according to age, receptor status and previous treatment was similar in both groups. Patients were examined at 3-month intervals, while bone scans and radiography of relevant lesions in the skeleton were performed every 6 months. After a median follow-up of 13 months, the morbidity in the treated group was significantly less than in the controls. This concerned the occurrence of hypercalcemia, bone pain and fractures, and the need for radiotherapy of osteolytic lesions. In this interim analysis, APD treatment more than halved the requirement for specific treatment of bone lesions. The treatment is simple and well tolerated at a relatively low dosage. A higher oral dose was precluded due to gastrointestinal toxicity. Because the effect of APD on skeletal morbidity was not complete, efforts should be made to develop more effective and less toxic bisphosphonates.
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PMID:Effect of long-term bisphosphonate treatment on morbidity due to bone metastases in breast cancer patients. 266 67

Bisphosphonates, associated with rehydration, became the treatment of choice of malignant hypercalcemia when it became apparent that these compounds normalized plasma calcium in most cases within a few days and with almost no side effects, and that their effect was prolonged. Dichloromethylene bisphosphonate and aminobisphosphonate, especially APD, were shown to inhibit bone resorption with no noticeable inhibition of bone formation, and were highly effective in the long-term treatment of Paget's disease. APD was used in almost 300 patients with malignant hypercalcemia published in the literature and has been used in the medical clinic at Lausanne for several years. When given to 14 patients with malignant hypercalcemia at the dose of 25 mg/day until plasma calcium became normal for two consecutive days, APD had to be given for 4-11 days, severe hypercalcemia needing longer treatment than mild hypercalcemia (Adami et al. 1982). When given for a fixed period of 6 days, again plasma calcium normalized in all patients, whether APD was given i.v. (30 mg/day, ten patients) or orally (1200 mg/day, ten patients) (Adami et al. 1985). Further shortening of the treatment to one single infusion given over 24 h did not decrease the efficacy, as long as high enough doses were given (Blomqvist 1986). For severe hypercalcemia of above 3.5 mmol/liter 60-90 mg had to be given, while 30-45 mg was sufficient in milder cases (Body 1984). Otherwise, mild, transient, and asymptomatic hypocalcemia could occur. Normalization of plasma calcium went along with clinical improvement, sometimes even with correction of coma. Renal function was improved, even when the initial plasma creatinine levels were up to twice normal. Hypercalcemia could reoccur, but the duration of the effect of APD (1 week to several months) depended among other things on the dose administered. The decrease in plasma calcium was accompanied by a decrease in urinary calcium and hydroxyproline, both showing inhibition of bone resorption. In the case of recurrency, the treatment could be repeated with almost unaltered efficacy, except in end-stage cancer disease. When given to 13 normocalcemic patients with bone metastases from breast cancer, hydroxyproline and urinary calcium again decreased. Bone pains and radiologic signs of metastatic bone resorption also showed significant improvement, although these latter effects could also be explained by the antitumoral treatment, in this uncontrolled open trial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Treatment of tumor-induced osteolysis by APD. 276 65

Twenty-eight patients with progressive symptomatic bone metastases from breast cancer received (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) 30 mg in 500 ml of 0.9% saline infused over 2 h every 14 days. No other systemic therapy for breast cancer was prescribed. All patients had progressed on at least one previous systemic treatment. APD was continued until the disease progressed. Patients were assessed for objective response by the UICC criteria. In addition, subjective response was determined by a pain questionnaire. Radiological evidence of bone healing with sclerosis of lytic disease (UICC partial response) was seen in 4 patients. The median duration of response was 10 months. Eleven patients had stable disease for at least 3 months (median 5 months) and 9 progressed. Symptomatic response occurred in 9 patients and 12 reported an improvement in quality of life. Treatment was tolerated well with no significant toxicity. In conclusion, long-term inhibition of bone destruction is possible with APD therapy alone and both subjective and objective responses are seen.
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PMID:Treatment of bone metastases from breast cancer with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). 321 73

This report is concerned with therapeutic studies utilizing new bisphosphonic acids on tumor-induced osteolytic metastases. The bone metastases on SD rats were induced by intraarterial and intraosseous transplantation of Walker carcinosarcoma 256 B ascites cells. The treatment was carried out using disodium-3-amino-1-hydroxypropylidene-1,1-bisphosphonate (ADP), diglycidyl-[3-(3, 3-bisphosphono-3-hydroxy-propylamino)-2-hydroxypropyl-]urazol++ +-Na2 (DDU) and 1,2,4-triglycidylurazol (TGU). The extent of bone metastases was determined by X-ray on the 5th and 10th days following tumor inoculation, as well as both microradiographically and histologically upon termination of the experiment. High dose DDU produced a clear reduction of the tumor osteolysis, but these positive results were surpassed using APD. The best results were achieved by pretreatment with APD 24 h prior to tumor inoculation.
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PMID:Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat. 394 49

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

Bone metastases are a common cause of morbidity in patients with breast cancer. In an open, phase II, non-comparative trial to investigate the effects of repeated infusions of pamidronate (Aredia) on pain, mobility, analgesic consumption, bone healing and bone metabolism, 69 patients with breast cancer and bone metastases received pamidronate 60 mg intravenously in 250 ml normal saline over 1 or 4 hours every 2 weeks for a total of 13 infusions, until either progressive disease or a serious adverse event. Improvement in pain score was seen in 33 of 54 evaluable patients (61%) as measured by a linear analogue pain scale, and in 28 of 56 evaluable patients (50%) as measured on a 6-point pain scale: 18 (30%) of 60 evaluable patients showed reduction in a 6-point analgesic score, while 28 patients (50%) showed some improvement in mobility, as assessed by a questionnaire. Sclerosis appeared in > 25% of bone lesions in 2 patients and in < 25% of bone lesions in 12 patients. Urinary calcium/creatinine ratios fell dramatically during therapy. One patient developed symptomatic hypocalcemia, 1 showed deterioration in pre-existing renal insufficiency. Fever occurred in 19% of patients, and less than 20% developed flu-like symptoms. We conclude that intravenous infusions of pamidronate at a dose of 60 mg every 2 weeks produces a marked reduction in pain in patients with extensive bone metastases from breast cancer.
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PMID:Role of pamidronate in the management of bone metastases from breast cancer: results of a non-comparative multicenter phase II trial. Aredia Multinational Cooperative Group. 753 92

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.
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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.
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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 effect of the rate of infusion of disodium aminohydroxypropylidene bisphosphonate (APD; CGP 23339A), an inhibitor of bone resorption, on urinary excretion of this agent was studied in a randomized open-label study in 20 cancer patients. Ten patients received 60 mg of APD over 4 h, and the remaining 10 patients received the same dose over 24 h. Urine collected during specified intervals for 72 h after the start of the infusion was analyzed by high-performance liquid chromatography for unchanged APD. Mild and transient adverse experiences were observed in 12 (60%) patients; the most common were headache, fever, and phlebitis at the infusion site. No clinically significant laboratory abnormalities were observed, and none of the experiences were serious enough to require discontinuation of treatment. Cumulative urinary excretion of APD was a linear function of time, increasing rapidly after both the 4- and 24-h infusions were started. The mean (+/- standard deviation) cumulative urinary excretion of APD was 51.1 +/- 13.0% of the dose in the 20 patients, 55.0 +/- 15.0% in the 10 patients given the 4-h infusion, and 47.2 +/- 9.9% in the 10 patients receiving the 24-h infusion. Thus, the rate of infusion of the 60-mg dose did not influence retention of APD at 72 h after the start of therapy. Similarly, the presence or absence of bone metastases did not influence cumulative urinary excretion or the retention of APD.
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PMID:Urinary excretion of aminohydroxypropylidene bisphosphonate in cancer patients after single intravenous infusions. 833 45


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