Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The palliation of bone pain is a common clinical problem once metastatic prostate cancer has escaped from hormonal control. This retrospective study compares the results of treatment using hemibody irradiation (HBI) at the Royal Marsden Hospital (27 cases) with isotope therapy using the bone-seeking isotope strontium-89 (89Sr) at Southampton General Hospital (51 cases). Prior to analysis patients were matched for potential prognostic factors (performance status, bone scan extent of disease, age, histology and duration of hormone response) to minimize the effect of treatment selection bias. Pain control assessed at 3 months was similar for HBI and matched 89Sr cases, with 63% and 52% respectively showing some benefit. Median survival was similar for these groups at 20 and 21 weeks respectively. The unmatched 89Sr group, which had more favourable prognostic factors, had a better outcome with 96% showing improvement in pain and with a median survival of 59 weeks. Subsequent univariate analysis demonstrated that performance status and extent of disease on bone scan were of overriding importance in determining outcome. Transfusion requirements were higher for the HBI group than for the matched 89Sr group (50% and 25% respectively) but other bone marrow toxicity was similar. Despite routine anti-emetic therapy 37% of patients treated with HBI had some nausea or vomiting. Although expensive, 89Sr appears as effective a treatment option as HBI. Response is most likely with either approach when patients have a good performance status and a limited extent of disease.
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PMID:Palliation of bone metastases in prostate cancer. Hemibody irradiation or strontium-89? 137 17

Radiation is an effective modality for palliation of osseous metastases. In patients with a limited number of lesions, local external beam irradiation is the most expedient method of delivering radiation therapy. Complete or partial relief of pain will occur in 80-90% of patients. When metastases are widespread or when new sites continue to appear, localized external irradiation becomes logistically difficult. In such cases, hemibody irradiation has been effective with an overall response rate of 85%. However, nausea, vomiting, diarrhea, and bone marrow and pulmonary toxicity may complicate therapy. In these cases, an effective alternative is systemic phosphorus-32 (32P) or strontium-89 (89Sr). Relief of pain in the range of 60-90% has been reported. Toxicity of 32P is largely that of bone marrow suppression, while 89Sr appears to be relatively marrow-sparing. In this review, we consider systemic 32P or 89Sr as viable options to external beam or hemibody irradiation in the presence of numerous bone metastases.
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PMID:The palliation of osseous metastasis with 32P or 89Sr compared with external beam and hemibody irradiation: a historical perspective. 247 19

The phase II clinical trial of a strontium (89Sr) chloride agent (SMS. 2P) was performed in 9 patients with painful bone metastases secondary to prostate cancer. After an intravenous administration, 89Sr circulated in the plasma and was rapidly cleared. Urinary excretion varied widely among the patients. No serious acute side effects were observed. A mild transient increase in pain was reported by 4 patients 2-4 days after administration, two of whom complained of mild nausea or vomiting. All symptoms improved and never became a clinical problem. There were some abnormal hematological parameters. In particular, a decrease in the platelet level seemed to be a marrow suppression due to 89Sr irradiation. It is difficult to discriminate between the effects of 89Sr and the progress of the disease using tumor markers. The pain level improved within 2 weeks after administration and the effect continued for at least 8 weeks, which improved the quality of life for these patients.
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PMID:[Phase II clinical trial of the radioactive strontium (89Sr) chloride agent, SMS. 2P for pain palliation in patients with prostate cancer with bone metastases]. 753 34

More than two-thirds of the patients with osseous metastases experience debilitating bone pain, requiring some form of pain relief. Analgesics are limited in their efficacy. Palliative application of hemi-body external beam radiation therapy in the treatment of multiple osseous metastases also is limited due to toxicity associated with large treatment ports. Intravenous injections of bone seeking radioisotopes are effective in the palliation of pain with fewer side effects. Forty-one patients with multiple osseous metastases due to prostate and breast cancer were treated with strontium chloride 89 (89Sr) at the department of radiation oncology, in a university hospital. A retrospective analysis of these patients indicated that all subjects had severe pain that diminished their quality of life. Most of these patients had multiple co-morbid factors. Many were on opioids leading to adverse effects such as nausea, constipation, and drowsiness that required additional medication. Objective findings and evaluation of the responses were not always available for all patients. Following treatmentwith 89Sr, over two-thirds of the patients responded favorably and required lower doses of opioids.
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PMID:Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience. 1215 27

Strontium ranelate is a novel therapy for the treatment of postmenopausal osteoporosis with actions to reduce bone resorption and increase bone formation. In vitro, strontium ranelate has anabolic and antiresorptive activity, increasing collagen and non-collagen protein synthesis, enhancing pre-osteoblast differentiation, inhibiting osteoclast differentiation, and reducing osteoclast function. In animal models, the increase in bone density is closely correlated with increases in biomechanical bone strength. Histomorphometry demonstrates reduced osteoclast surfaces with increased bone formation. Clinical trials in postmenopausal women have demonstrated 3-year fracture efficacy. Reductions in vertebral fracture were seen in patients with and without prevalent vertebral fracture. Nonvertebral fractures were also significantly reduced. In a subgroup of patients at high risk for hip fracture, there was a significant reduction in hip fracture risk. Strontium ranelate is well tolerated with nausea, diarrhea, headache, and dermatitis more frequent in treated patients only for the first 3 months of therapy. Together, these data suggest that strontium ranelate is a well-tolerated and effective therapy for postmenopausal osteoporosis reducing vertebral and nonvertebral fracture by a novel dual antiresorptive and anabolic action on bone.
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PMID:Strontium ranelate--data on vertebral and nonvertebral fracture efficacy and safety: mechanism of action. 1652 6

Strontium ranelate is a new orally administered agent for the treatment of women with postmenopausal osteoporosis that reduces the risk of vertebral and hip fractures. Evidence for the safety and efficacy of strontium ranelate comes from two large multinational trials, the SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment Of Postmenopausal Osteoporosis) studies. The SOTI study evaluated vertebral fracture prevention in 1649 postmenopausal women with a mean age of 69 y. The subjects all had at least one previous vertebral fracture and a low spine bone mineral density (BMD) (equivalent to a Hologic spine T-score below -1.9). The strontium ranelate group had a 41% lower risk of a new vertebral fracture than the placebo group over the three-year study period (relative risk [RR] = 0.59; 95% confidence interval [CI]: 0.48-0.73; p < 0.001). The TROPOS study evaluated non-vertebral fracture prevention in 5091 postmenopausal women with a mean age of 77 y. The subjects were aged 74 y and over (or 70-74 y with one additional risk factor) and a low femoral neck BMD (equivalent to an NHANES III [Third National Health and Nutrition Examination Survey] T-score below -2.2). Over the three-year study period there was a 16% reduction in all non-vertebral fractures (RR = 0.84; 95% CI 0.702-0.995; p = 0.04) and a 19% reduction at the principal sites for non-vertebral fractures. The TROPOS study was not powered to investigate hip fracture risk. However, in a high risk group of women aged 74 y and over and with an NHANES III femoral neck T-score less than -2.4 there was a 36% reduction in hip fracture risk (RR = 0.64; 95% CI: 0.412-0.997; p = 0.046). The overall incidence of adverse events did not differ significantly from placebo and were generally mild and transient, the most common being nausea and diarrhea. Strontium ranelate is a useful addition to the range of anti-fracture treatments available for treating postmenopausal women with osteoporosis and is the only treatment proven to be effective at preventing both vertebral and hip fractures in women aged 80 y and over.
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PMID:Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review of safety and efficacy. 1804 14

Because no comparative studies exist, no clear pronouncements can be made about the potential differences in effectiveness and safety between PTH 1-34 and PTH 1-84. As regards the efficacy, a convincing reduction of vertebral fractures was shown in both cases [Neer, R.M., Arnaud, C.D., Zanchetta, J.R., Prince, R., Gaich, G.A., Reginster, J.Y., Hodsman, A.B., Eriksen, E.F., Ish-Shalom, S., Genant, H.K., Wang, O., Mitlak, B.H., 2001. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434-1441; Greenspan, S.L., Bone, H.G., Ettinger, M.P., Hanley, D.A., Lindsay, R., Zanchetta, J.R., Blosch, C.M., Mathisen, A.L., Morris, S.A., Marriott, T.B., Treatment of Osteoporosis with Parathyroid Hormone Study Group, 2007. Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann. Intern. Med. 146, 326-339]. A reduction of non-vertebral fractures was shown in the case of PTH 1-34 only. Another significant resemblance is that both medicines have a strong anabolic action; this mechanism of action is essentially different from the bisphosphonates and strontium ranelate. Both medicines constitute a welcome addition to the therapeutic arsenal for patients with severe osteoporosis. More data from literature (including information on follow-up data and use in men) are available for PTH 1-34 because it has been available for longer. As regards the side effect profile, PTH 1-84 appears to have a higher incidence of hypercalcemia, hypercalciuria and nausea than teriparatide. Here, too, no comparative study exists: the differences may therefore be based on an actual difference in side effects, or it may be ascribed to differences in definitions and/or patient populations.
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PMID:PTH-analogs: comparable or different? 1912 66

This is a review of the pharmacology of strontium ranelate (Protelos, Protos, Protaxos, Bivalos, Osseor), and its efficacy and tolerability in the treatment of patients with postmenopausal osteoporosis. Strontium ranelate is a divalent strontium salt of ranelic acid that is capable of increasing bone formation and reducing bone resorption, thereby uncoupling and rebalancing bone turnover in favour of bone formation. The drug is effective in reducing the risk of fractures, including both vertebral and nonvertebral fractures, in patients with postmenopausal osteoporosis, according to data from two large, double-blind, placebo-controlled, multicentre trials of 5 years' duration, and reduced the risk of hip fracture in high-risk patients in a post hoc analysis of one trial. Moreover, data from patients who continued to receive the drug during the 3-year extension phases of these trials indicate that strontium ranelate continues to provide protection against new vertebral fractures and nonvertebral fractures for up to 8 years of therapy. It also improves bone mineral density at numerous sites and both increases markers of bone formation and decreases markers of bone resorption. Strontium ranelate is administered orally as a suspension and is generally well tolerated. The nature of adverse events was generally similar regardless of treatment duration in clinical trials, with the most commonly reported being nausea and diarrhoea over 5 years of treatment, and memory loss and diarrhoea during longer-term treatment. Although an increased risk of venous thromboembolism was associated with strontium ranelate relative to placebo over 5 years of treatment in a pooled analysis of clinical trials, postmarketing data have not confirmed this finding. Overall, the clinical data available suggest that strontium ranelate is an effective and generally well tolerated option for the first-line treatment of postmenopausal osteoporosis.
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PMID:Strontium ranelate: a review of its use in the treatment of postmenopausal osteoporosis. 2039 57

This is a review of the pharmacology of strontium ranelate (Protelos, Protos, Protaxos, Bivalos, Osseor), and its efficacy and tolerability in the treatment of patients with postmenopausal osteoporosis. Strontium ranelate is a divalent strontium salt of ranelic acid that is capable of increasing bone formation and reducing bone resorption, thereby uncoupling and rebalancing bone turnover in favour of bone formation. The drug is effective in reducing the risk of fractures, including both vertebral and nonvertebral fractures, in patients with postmenopausal osteoporosis, according to data from two large, double-blind, placebo-controlled, multicentre trials of 5 years' duration, and reduced the risk of hip fracture in high-risk patients in a post hoc analysis of one trial. Moreover, data from patients who continued to receive the drug during the 3-year extension phase of these trials indicate that strontium ranelate continues to provide protection against new vertebral fractures and nonvertebral fractures for up to 8 years of therapy. It also improves bone mineral density at numerous sites and both increases markers of bone formation and decreases markers of bone resorption. Strontium ranelate is administered orally as a suspension and is generally well tolerated. The nature of adverse events was generally similar regardless of treatment duration in clinical trials, with the most commonly reported being nausea and diarrhoea over 5 years of treatment, and memory loss and diarrhoea during longer-term treatment. Although an increased risk of venous thromboembolism was associated with strontium ranelate relative to placebo over 5 years of treatment in a pooled analysis of clinical trials, postmarketing data have not confirmed this finding. Overall, the clinical data available suggest that strontium ranelate is an effective and generally well tolerated option for the first-line treatment of postmenopausal osteoporosis.
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PMID:Spotlight on strontium ranelate: in postmenopausal osteoporosis. 2080 66

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.
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PMID:Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis. 2163 97


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