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)

Selective aspects of quality of life during supportive pamidronate (APD) treatment were assessed in breast cancer patients with osteolytic metastases. 144 patients were randomised to a pamidronate group (n = 76) or a control group (n = 68). A questionnaire measuring mobility impairment, bone pain, fatigue and gastrointestinal toxicity was administered at 3-monthly intervals. The analysis focused on changes in these quality of life domains over time. The median follow-up for both groups was 18 months. Mobility impairment and bone pain were significantly less in the pamidronate group as compared with the control group, due primarily to a rapid improvement shortly after initiation of pamidronate treatment. Thereafter, a gradual increase in these symptoms was noted in both groups. Gastrointestinal complaints and fatigue levels were similar over time in the two groups, suggesting that these symptoms are more dependent on disease-related events and cytotoxic treatment than on pamidronate treatment. The results indicate that reduced skeletal morbidity in breast cancer patients during pamidronate treatments is associated with an improvement in selective aspects of quality of life.
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PMID:The effect of supportive pamidronate treatment on aspects of quality of life of patients with advanced breast cancer. 167 65

The search into the way in which skeletal metastases develops has not only shown that there are several mechanisms for the progressive bone destruction and bone formation that occur simultaneously in the majority of skeletal metastases, but also that an understanding of these basic mechanisms has significant therapeutic implications. Our results have shown that there are two main mechanisms for the bone formation: stromal bone formation and reactive bone formation. The former occurs in tumours which tend to be acellular, with a large fibrous stroma, whereas the latter occurs in virtually all metastases. There is no difference in the basic pathological process of sclerotic or lytic metastases, the radiographic appearance purely indicating the net balance between the different types of bone formation and the simultaneous progressive bone destruction. An understanding of the pathophysiological response to skeletal metastases explains why skeletal scintigraphy can be used to diagnose these lesions and the different mechanisms underlying the 'three-phase scintigram'. The first phase indicates the vascularity of the lesion; the second phase or 'blood-pool' image indicates the concentration in the extracellular fluid and the third phase or 'skeletal or delayed image' indicates the uptake in the reactive new bone. The secretion of an osteoblast inhibiting factor by myeloma indicates why there is no reactive bone produced by the majority of lesions in the absence of a fracture, and why scintigraphy is less reliable than plain radiographs for the detection of the lesions. There are two main mechanisms for the bone destruction, the most important being mediated via osteoclasts. An understanding of the humoral mechanisms stimulating the osteoclast proliferation may lead to more effective treatment of malignant hypercalcaemia and lytic metastases. Early results of use of APD are encouraging, and our results also suggest that clinical trials should be established to evaluate the effect of combination therapy with APD or prostaglandin inhibitor combined with the agents normally used in the management of patients with disseminated mammary carcinoma. The development of treatments to inhibit tumour-induced osteolysis will minimise the complications of pathological fracture, spinal instability, etc., and even if these treatments do not affect the primary tumour, its ability to metastasize, or the patient's survival, such treatment will be a major advance in the management of patients with carcinoma, because of the significant morbidity currently associated with the development of skeletal metastases and their complications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The development of skeletal metastases. 279 40

The distribution of 14C-APD and 99mTc-APD (APD = 3-amino-1-hydroxypropane-1,1-diphosphonic acid) in untreated rats and in rats bearing intratibially transplanted osteosarcomas was investigated autoradiographically and scintigraphically. Also investigated was the effect of high doses of APD on survival time and tumor growth of osteosarcoma-bearing rats. Intravenous administration of APD resulted in high rates of APD accumulation in bones, tumor tissue and pulmonary metastases as well as in dose-related accumulation in the liver. No significant increase in the median survival time of tumor-bearing animals was achieved at the two dosage schemes tested, i.e. 2 X 23.5 mg/kg and 10 X 11.75 mg/kg APD. The growth of primary tumors was slightly increased by administration of APD. The chemosensitivity of the transplantable osteosarcoma model was demonstrated by comparison with dacarbazine-treated control animals.
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PMID:Distribution of 3-amino-1-hydroxypropane-1,1-diphosphonic acid in rats and effects on rat osteosarcoma. 386 53

An aromatic retinoic acid analogue (Ro 10-9359) previously shown to be capable of inhibiting the growth and metastasis of immunogenic sarcomas and carcinomas (see accompanying paper) was tested for its anti-tumour effects in various categories of immune-deprived mice. 'Non-specific' immunosuppression evoked by sub-lethal whole-body X-irradiation abolished the inhibition of tumour growth induced by Ro 10-9359 in immunocompetent syngeneic hosts. Also, retinoid treatment of three categories of T-lymphocyte-deprived mice (nu/nu; thymectomized-irradiated; and cyclosporin A-treated) was ineffective in reducing the local growth rate or inhibiting spontaneous metastasis of their tumours; in fact, regardless of retinoid treatment the tumours grew faster and metastasized more widely in immunosuppressed animals than in controls. Silica and carrageenan (which are toxic to mononuclear phagocytes) did not interfere with the inhibitory effects of Ro 10-9359 on tumour growth, and did not themselves potentiate metastasis; however, both agents prevented the abolition of DM6 carcinoma metastasis by retinoids. APD, which inhibits the 'accessory cell' function of macrophages did not reduce the effectiveness of Ro 10-9359 against local tumours. However, in contrast to silica and carrageenan this agent did increase the incidence of metastasis of DM6 carcinoma from 40% to 60%, but in the presence of retinoids only 20% of mice succumbed to secondary disease. These results suggest an essential role for T lymphocytes in retinoid-induced local tumour growth inhibition, and a further contribution of mononuclear phagocytes to the prevention of metastatic disease.
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PMID:Inhibition of growth and metastasis of syngeneic transplantable tumours by an aromatic retinoic acid analogue. 2. T cell dependence of retinoid effects in vivo. 388 26

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

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

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

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


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