Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty five hormone manipulated patients with prostate cancer and metastatic bone disease, treated at least 6/12 previously by hormone manipulation, were given intravenous infusions of Disodium Pamidronate (APD) over a 6 month period. Patients received 30 mg weekly for 4 weeks then twice monthly for 5 months. No other treatment was administered during study. Eleven of 17 patients with pain at the start of the study were pain free at the end. Fasting morning calcium excretion and serum osteocalcin fell significantly with Pamidronate (P less than 0.0001) and urine hydroxyproline was lowered in 13/20 evaluable patients at 6 months. Alkaline phosphatase fell in a proportion of patients and five of 17 patients with previously progressive bone scans stabilised (4) or regressed (1) on treatment. Rising acid phosphatase levels were also lowered in five patients. It is concluded that Pamidronate may be effective in palliating bone pain in some patients and has a stabilising influence on abnormally high bone turnover in metastatic prostate cancer. Further controlled studies of the compound are now warranted.
 ...
PMID:Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study. 200 84

Bisphosphonates are the treatment of choice in tumor-induced hypercalcemia. Pamidronate (Aredia) is effective in this indication, but few studies have addressed the question of its dose-effect relationship. Review of the published literature suggests that a clinically relevant dose-response relationship exists in the dose range 30-60 mg; most hypercalcemic patients will achieve normocalcemia with a dose of 60 mg pamidronate or more. More recent publications have reported the emerging role of bisphosphonates in the treatment of malignant osteolytic bone disease. Several non-randomized studies have shown beneficial effects from continuous administration of clodronate or pamidronate, though the magnitude of such effects was moderate. Two dose escalation trials with pamidronate showed that regimens with a dose intensity below 20 mg/week and single doses of 30 mg or less were ineffective. One randomized, prospective study compared pamidronate 60 mg with 90 mg given intravenously every 3 weeks. Both regimens showed a significant palliative effect. Patients treated with 90 mg had a greater reduction in pain intensity compared to those receiving 60 mg. Optimal schedules for different patient populations require further investigation.
 ...
PMID:Progress in the treatment and palliation of advanced breast cancer: does the dose of pamidronate determine its effects? 753 93

Pamidronate is a second generation bisphosphonate that has been used in Europe for the treatment of Paget's disease of bone for several years. It relieves pain and reduces bone turnover in Paget's disease. To assess the effects of pamidronate on Paget's disease of bone, the authors treated 28 patients, aged 45 to 87, with longstanding Paget's disease for a period of 4-18 months. Parameters measured included pain and serum alkaline phosphatase, urinary hydroxyproline, and ionized calcium concentrations. Patients were organized into two groups. Patients in the first group had initial alkaline phosphatase concentrations below 215 U/L, which decreased to normal after one dose of pamidronate. Patients in this group also experienced symptomatic improvement. Patients in the second group had initial alkaline phosphatase values greater than 240 U/L, which did not normalize after 2-11 pamidronate infusions. More patients in this latter group did not report symptomatic improvement. Patients in the second group also had a higher incidence of hypocalcemia. It is concluded that there is a clear relation between initial alkaline phosphatase level in Paget's disease and response to treatment with pamidronate. The authors' current protocol for treating patients with pamidronate is based on this relation. Because pamidronate proved most effective when used in mild Paget's disease, therapy probably should be instituted early in the course of disease.
 ...
PMID:Effects of intravenous pamidronate therapy on Paget's disease of bone. 794 81

Tumor-induced hypercalcemia (TIH) and tumor-induced osteolysis (TIO) are essentially due to a marked increase in osteoclast-mediated bone resorption. Parathyroid-hormone-like protein plays an essential role in TIH, and maybe in TIO, but other substances, such as growth factors or cytokines, could contribute to the osteoclast activation and osteoblast inhibition secondary to the neoplastic infiltration of the skeleton. Treatment of TIH essentially consists of volume repletion and administration of potent anti-osteolytic drugs. Intravenous administration of the bisphosphonate clodronate or pamidronate is particularly useful for this. Pamidronate at a dose of 1.0-1.5 mg/kg as a single 4- to 24-h infusion can normalize serum calcium in about 90% of hypercalcemic cancer patients. The apparently low response rate of bone metastases to systemic antineoplastic therapy seems essentially to reflect the relative insensitivity of our current methods for assessing response in TIO. Quantitative evaluation of pain and of newly developed biochemical markers of bone turnover could be particularly useful for early assessment of response. Prolonged administration of oral pamidronate could reduce by almost one-half the complications of TIO, and iterative bisphosphonate infusions could induce a dramatic relief of bone pain in one-third and a sclerosis of lytic lesions in one-fourth of the cases. These data must, however, be confirmed in randomized blind trials and many questions remain unanswered concerning the optimal therapeutic schemes. Despite these limitations, medical therapy of TIO by non-cytotoxic means has already become a reality.
 ...
PMID:Medical treatment of tumor-induced hypercalcemia and tumor-induced osteolysis: challenges for future research. 814 98

The authors treated 18 patients with Paget's disease of bone (12 men and 6 women, age 65 +/- 5 years) with pamidronate (bisphosphonate of the second generation). Three patients from this group were treated previously without success with calcitonin or bisphosphonate of the first generation (etidronate) 50% of the patients suffered from the polyostotic form of the disease. In one patient a rare combination of primary hyperparathyroidism with Paget's bone disease was found and in another patient later an osteosarcoma developed in the affected bone. To all patients sodium pamidronate was administered (Aredia, Ciba-Geigy) 30 mg per day by i.v. infusion for 2 hours during three days. Four patients developed fever, two patients phlebitis at the site of injection. These side-effects are described by the manufacturer. Two patients developed transient regional alopecia, not described so far. Subjective pain relief of the affected skeleton occurred in one patient after one month of treatment, after three months in 78%. Laboratory manifestations of activity of the disease (serum activity of alkaline phosphatase, tartrate resistant acid phosphatase and hydroxyprolinuria) declined gradually from the 1st to the 6th month after onset of treatment. There was a less marked decline of the osteocalcin serum concentration. The concentration of calcium, phosphorus and vitamin D metabolites did not change markedly. Twelve months after treatment 14.7% of the patients were inactive according to laboratory tests, 73% however experienced another rise of parameters of osteoresorption and osteoformation. Pamidronate treatment in patients with Paget's disease of bone is effective and safe.
 ...
PMID:[Paget's disease of bone and treatment with pamidronate]. 837 65

Diphosphonates are potent inhibitors of bone resorption, they have been evaluated in several clinical trials for bone metastases. We performed a clinical study to evaluate the therapeutic effect of Disodium Pamidronate over pain and radiologic evolution in bone metastases (Breast Cancer and Multiple Myeloma patients). The results regarding the first 10 patients concluded that there is good drug tolerability and significant analgesic activity in 6 patients, with sclerosis of lytic skull lesions in one breast cancer patient.
 ...
PMID:[Disodium pamidronate (APD) in the treatment of bone metastases]. 848 64

Pamidronate is a potent biphosphonate which modulates tumour-induced osteolysis (TIO) by inhibiting osteoclast-mediated bone resorption. In a phase II trial, 69 breast cancer patients with symptomatic progressive bone metastases were given infusions of pamidronate 60 mg over 1 or 4 h every 2 weeks for a maximum of 13 infusions or until progressive disease (PD) at any site. No other systemic anticancer therapy was allowed. Pain was measured using a visual analogue scale, mobility using a detailed eight-point questionnaire and analgesic intake using a six-point scale. Improvements in pain, mobility and analgesic scores occurred in 61, 50 and 30% of patients, respectively, with 33, 21 and 16% achieving a 40% improvement for > or = 8 weeks. At trial discontinuation, baseline levels of pain and mobility had improved by 27% (P = 0.001) and 20% (P = 0.004), respectively, despite a one category reduction in analgesic intake in 27% of patients. Using this relatively high dose of pamidronate, symptomatic response was independent of the number of bone metastases and also of infusion rate. The infusions were well tolerated with no major toxicities reported. Pamidronate infusions provide useful palliation for breast cancer patients with symptomatic bone metastases.
 ...
PMID:Pamidronate infusions as single-agent therapy for bone metastases: a phase II trial in patients with breast cancer. 856 51

We have evaluated the value of specific bone resorption markers in monitoring metastatic bone disease to define the duration of action of a single high-dose pamidronate infusion. Twenty patients received a single infusion of pamidronate 120 mg for painful bone metastases. Ten out of these 20 patients also received a second infusion. They were evaluated at baseline, 2, 4 and 8 weeks after each infusion. A composite pain questionnaire, serum and urine tests were carried out at these time points. Bone resorption markers measured included urinary calcium, hydroxyproline and two new markers: pyridinoline and deoxypyridinoline. Reference values were defined by 20 healthy controls matched by age and sex. Pamidronate induced a profound fall in bone resorption with a maximal effect within the first month after therapy. Changes in urinary calcium levels were confounded by a rise of 100% in the parathyroid hormone levels. Before treatment, pyridinoline and deoxypyridinoline were increased in 70% of patients, while urinary calcium was increased in only 40% of them. Thirteen patients had a > or = 50% fall in deoxypyridinoline levels and were considered as biochemical responders. These patients had a mean reduction in pain score of about 30% of baseline levels, which was significantly higher than the seven non-biochemical responders. In conclusion, urinary calcium is not a precise marker of bone resorption. Deoxypyridinoline seems to be the most specific bone resorption marker in cancer patients. Biochemical responders have the most benefit from pamidronate in terms of pain relief. This suggests that patients may benefit from more potent or repeated infusions of bisphosphonates.
 ...
PMID:Metabolic effects of pamidronate in patients with metastatic bone disease. 862 69

An intravenous dosage schedule using pamidronate disodium, based on biochemical severity, was used to treat 71 patients with Paget's disease who had no previous bisphosphonate treatment. Disease severity was stratified by fasting hydroxyproline excretion (HypE): Group (Gp) I (mild disease; HypE < 5.0 mumol/LGF) received a total dose of 120 mg; Gp II (moderate; HypE 5.00-9.99) received 180 mg; and Gp III (severe; HypE > or = 10) received 240 mg. Within each group patients were randomly allocated to receive daily 30 mg or 60 mg infusions. Observations for 2 years included pain scores, indices of bone turnover, and radiology of lytic lesions. There was no difference in biochemical responses, or in the percentage of patients with early fever, between the 30 mg and 60 mg daily subgroups; for convenience, 60 mg infusions are recommended. Neutrophils and total white cell counts were both significantly below baseline 4 days after the first infusion; lymphocytes were significantly reduced by day 2; and all three measures had returned to within the reference range by day 6. Remission was assessed at 6 months, when both plasma alkaline phosphatase (ALP) and HypE had reached stable nadirs. Increasing severity was associated with increasing resistance to suppression of HypE at 6 months to within the reference range: Gp I, 87%; Gp II, 44%; and Gp III, 0% (p < 0.0001 by chi-square test). Biochemical relapse at 2 years (defined as ALP 50% above the 6 month level) was also dependent on initial disease severity (Gp I, 6%; GpII, 39%; Gp III, 62%; p < 0.0005 by chi-square test). There was no association between time to relapse and either initial dose or log dose. Radiologic lytic lesions (in 22 patients) were all in remission at 3 months; however, relapse rates at 2 years appeared to be severity-dependent: Gp I, 13%; Gp II, 43%; and Gp III, 57% (n.s. by chi-square test). Remission rates based on a fall to < 50% of pretreatment of either HypE or ALP were more in accord with lytic lesion remission rates than were rates based on HypE falling to within the reference range. Pamidronate produced a significant reduction from baseline in Pagetic bone, Pagetic joint, and unrelated musculoskeletal pain in the first 6 months (p < 0.0001). From 0 months to 2 years the maintenance of improvement in bone pain (p < 0.005) and joint pain (p < 0.05) was significantly better than in unrelated pain. Pamidronate is a safe, welltolerated, and effective treatment for Paget's disease. In spite of larger dosage in severe disease, increasing severity was associated with resistance to normalization of biochemistry and a higher incidence of biochemical and radiological relapse at 2 years. Our current dosage recommendation would be for two 60 mg infusions for mild disease (Gp I); and four 60 mg infusions for moderate disease (Gp II). Severe disease (Gp III) remains a challenge; regardless of dosage, the majority of patients will be in relapse 2 years after a single course of treatment.
 ...
PMID:Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: a 2-year study. 889 45

Basic guidelines for cancer pain treatment can be found in many different handbooks published in the last years. Particularly those of the World Health Organisation published in 1986 and revised in 1996, furnish useful indication for cancer pain treatment. The authors therefore focused on resuming the most recent development in this field. In the research regarding alternative routes of administration of opioids in alternative to the oral route, the rectal administration of morphine and methadone and the transdermal route for fentanyl have proved to be efficacious. The subcutaneous route (for morphine) as well as the intravenous, peridural and subaracnoid routes, being known for some time are not taken in consideration in this paper. Various studies suggest that alternative routes are necessary in 53-70% of patients in their last days or months of live. The most frequent causes for the need to stop oral administration are dysphagia, nausea, and uncontrollable vomiting, bowel obstruction, malabsorption, cognitive failure, coma, and pain syndromes requiring anaesthetics which need be administered via the spinal route. Among the drugs, tramadol seems to be effective in the control of moderate pain. Tramadol is a centrally acting analgesic drug; it has an agonist effect on mu 1 receptors of opioids and acts also by inhibiting the re-uptake of noradrenaline and serotonine which activates descending monoaminergic inhibitory pathways. Recent clinical studies revealed that pamidronate has an analgesic effect in pain due to bone metastasis. Pamidronate is part of the biphosphonates, which are active on bone metabolism and are usually being used for the treatment of hypercalcaemia in cancer. The authors also describe briefly the indication of ketamin in association with morphine for the treatment of neuropathic pain.
 ...
PMID:[Treatment of pain in oncology]. 923 25


1 2 3 4 5 Next >>