Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe hypercalcemia is a life-threatening medical emergency. It is most commonly caused by malignant tumors, but can also be caused by primary hyperparathyroidism or less often by a dysregulated production of active vitamin D in granulomatous disorders. Symptoms include nausea, vomiting, renal insufficiency, severe dehydration, lethargy, confusion, and even coma. Severity of symptoms, calcium concentrations, and the overall status of the patient are important considerations in selecting appropriate therapy. Hydration to correct volume depletion is the cornerstone of acute therapy. Loop diuretics may be added to saline hydration after extracellular fluid volume has been replenished to enhance urinary calcium excretion and mitigate fluid overload from rehydration. Calcitonin and intravenous infusion of bisphosphonates reduce serum calcium levels by interfering with calcium release from the skeleton. Dialysis with a low or zero calcium dialysate is reserved for patients who are refractory to these measures. Corticosteroids are effective with hypercalcemia due to increased vitamin D levels and in multiple myeloma.
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PMID:[Hypercalcemic crisis]. 1468 84

(1) First-line treatment of multiple myeloma depends first and foremost on the patient's age. There is no standard treatment for relapses and the median survival time after the first relapse is only 12 to 15 months. (2) Bortezomib, a cytotoxic agent, inhibits the 26S proteasome involved in protein breakdown in mammalian cells. It is licensed for use in myeloma after multiple treatment failure. (3) Three dose-finding studies showed some effects of 1 mg/m2 and 1.3 mg/m2 bortezomib administered twice a week for two weeks, with each course followed by a 10-day treatment-free period. It is not known whether 1.3 mg/m2 is more effective than 1 mg/m2. (4) In a non comparative trial that included 202 patients with multidrug-resistant myeloma, progression-free survival time increased to a median of 6.6 months (compared to 3.3 months after previous relapses), and the median overall survival time was 7 months in the 75% of patients who did not respond and more than 15 months in the 25% of responders. However, given the heterogeneous nature of the study population the evidence from this trial is rather weak. (5) An unblinded comparative trial including 54 patients failed to show whether bortezomib 1.3 mg/m2 was more effective than bortezomib 1 mg/m2 in terms of clinical outcome. Another comparative trial including 669 patients indicated that bortezomib was more effective than dexamethasone in terms of the median time to disease progression (5.7 months versus 3.6 months). (6) Animal studies indicate that bortezomib is cardiotoxic and neurotoxic, and that the interval between the maximal tolerated dose and the fatal dose is very small. Experience with bortezomib use is too limited to know the possible clinical repercussions of these experimental findings. (7) Adverse effects were frequent and varied in clinical trials. They included fatigue, nausea and vomiting, diarrhea, anemia, thrombocytopenia and peripheral neuropathies. They affected 30% to 60% of patients overall, and were severe in about 10% to 20% of patients. Other adverse effects included hypotension, fever, headache, pain and dehydration. (8) Bortezomib is metabolised by cytochrome P 450 isoenzyme 3A4, and this implies a high risk of drug-drug interactions. (9) Each vial of bortezomib contains more of the drug than is needed for one injection. This is not only wasteful, but also carries a risk of overdosing, with potentially serious consequences, should the entire contents be injected by mistake. (10) Bortezomib may be used as a last resort in some patients with multiple myeloma, but the individual risk-benefit balance must be carefully weighed in each case.
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PMID:Bortezomib: new drug. A last resort in myeloma: modest efficacy, major risks. 1598 89

An increasing number of diagnostic imaging procedures requires the use of intravenous radiographic contrast agents, which has led to a parallel increase in the incidence of contrast-induced nephropathy. Risk factors for development of contrast-induced nephropathy include pre-existing renal dysfunction (especially diabetic nephropathy and multiple myeloma-associated nephropathy), dehydration, congestive heart failure and use of concurrent nephrotoxic medication (including aminoglycosides and amphotericin B). Because contrast-induced nephropathy accounts for a significant increase in hospital-acquired renal failure, several strategies to prevent contrast-induced nephropathy are currently advocated, including use of alternative imaging techniques (for which contrast media are not needed), use of (the lowest possible amount of) iso-osmolar or low-osmolar contrast agents (instead of high-osmolar contrast agents), hyperhydration and forced diuresis. Administration of N-acetylcysteine, theophylline, or fenoldopam, sodium bicarbonate infusion, and periprocedural haemofiltration/haemodialysis have been investigated as preventive measures in recent years. This review addresses the literature on these newer strategies. Since only one (nonrandomized) study has been performed in intensive care unit patients, at present it is difficult to draw firm conclusions about preventive measures for contrast-induced nephropathy in the critically ill. Further studies are needed to determine the true role of these preventive measures in this group of patients who are at risk for contrast-induced nephropathy. Based on the available evidence, we advise administration of N-acetylcysteine, preferentially orally, or theophylline intravenously, next to hydration with bicarbonate solutions.
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PMID:Bench-to-bedside review: preventive measures for contrast-induced nephropathy in critically ill patients. 1613 85

Hypercalcemia associated with malignancies is reported in up to 20 to 30% of patients with cancer during the course of the disease, and points to a poor prognosis. Symptoms related to the central nervous system, as progressive mental impairment, stupor and coma, predominate. Alterations in kidney function (water-concentrating defect leading to polyuria) and gastrointestinal tract (anorexia, nausea, vomiting) corroborate to dehydration and a further increase in serum calcium. Cancer-induced hypercalcemia may be classified as: 1) local osteolytic hypercalcemia (LOH), due to marked increase in osteoclastic bone resorption in areas surrounding the malignant cells within the marrow space; 2) humoral hypercalcemia of malignancy, caused by the secretion of parathyroid hormone-related protein (PTHrP) by the malignant tumor; 3) ectopic hyperparathyroidism; 4) 1,25(OH)2 D-secreting tumors. Adequate control of hypercalcemia is necessary to give the patient time to respond to anti-cancer therapy. Volume expansion with saline will correct dehydration, improve glomerular filtration and increase urinary calcium excretion, which may be further stimulated by loop diuretics. Intravenous bisphosphonates are the most effective agents to control hypercalcemia, as they block osteoclastic osteolysis and also have antitumoral effects, decreasing bone metastases. New approaches to control the skeletal manifestations of malignancies are anti-PTHrP and anti-RANKL antibodies, osteoprotegerin, and also proteasome inhibitors in the case of multiple myeloma.
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PMID:[Hypercalcemia of malignancy: clinical features, diagnosis and treatment]. 1644 66

Multiple mycloma causes a disproportionate amount of the malignancy-related renal insufficiency. Acute renal insufficiency in myeloma patients can occur due to dehydration, hypercalcemia, side effects of medications (NSAIDs) or tumor lysis syndrome in addition to cast nephropathy, amyloidosis and light chain deposition disease. Patients on hemodialysis have traditionally been excluded from antineoplastic therapy due to fear of side effects and lack of studies addressing benefit. Melphalan is the most effective chemotherapeutic agent in myeloma and its PK (pharmacokinetics) are not adversely affected by impaired renal function. Because of more pronounced toxicity of Melphalan 200 mg/m2 conditioning regimen, Melphalan 140 mg/m2 has become the standard of care. 24% of patients become dialysis-independent at a median of 4 months after autotransplantation. Favorable factors for becoming dialysis independent were duration of dialysis <or=6 months and pretransplant creatinine clearance >10 ml/min. While no good data are available on the use of thalidomide in the presence of renal failure, it is our experience that severe neuropathy, constipation, lethargy and bradycardia are more frequent in patients with creatinine >or=3 mg/dl. It has become apparent that bisphosphanates-zoledronic acid more than pamidronate-cause renal dysfunction. If patients remain dialysis-dependent after autotransplantation, we recommend to delay considering a renal transplant until at least 3 years after the first transplant.
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PMID:High-dose therapy in patients with plasma cell dyscrasias and renal dysfunction. 1707 30

A Phase I trial (NCT00109109) of oral vorinostat 200, 250 or 300 mg twice daily for 5 days/week/4-week cycle or 200, 300, or 400 mg twice daily for 14 days/3-week cycle until progressive disease or intolerable toxicity was conducted. Patients with measurable, relapsed/refractory multiple myeloma were eligible. The objectives were to determine maximum tolerated doses (MTDs) and assess activity and safety. Thirteen patients (median age, 63 years; median prior therapies, 3) were enrolled. MTDs were not determined due to early study termination by sponsor decision. One patient (250 mg twice daily 5 days/week) developed dose-limiting toxicity (DLT; grade 3 fatigue). There were no other DLTs and the maximum administered doses were 250 mg twice daily for 5 days/week/4-week cycle and 200 mg twice daily for 14 days/3-week cycle. Drug-related adverse experiences included fatigue, anorexia, dehydration, diarrhea, and nausea and were mostly grade <or=2. Of 10 evaluable patients, 1 had a minimal response and 9 had stable disease, demonstrating modest single-agent activity in relapsed/refractory multiple myeloma.
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PMID:Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma. 1829 14

Multiple myeloma (MM) is malignant disease caused by proliferation of malignant clone of terminally differentiated plasma-cells. Clinical features may include symptoms of bone disease, unexplained back-pain, fractures, anaemia, kidney failure, oedema, hypercalcaemia, bacterial infections, impaired hemostasis, peripheral neuropathy and hyperviscosity. Impairment of renal function occurs in 50% of patients with different forms of kidney disease. Majority of patients have precipitation of monoclonal immunoglobulins or their fragments in kidney. Hypercalcemia, dehydration, infections and nephrotoxic drugs contribute to development of kidney injury. Treatment consists of chemotherapy for primary disease, with plasma exchange in cases of hyperviscosity. Supportive treatment should include rehydration, treatment of hyperuricemia and hypercalcaemia. Patients with end-stage renal disease could be treated with peritoneal dialysis or haemodialysis. Renal transplantation is rarely offered to this group of patients.
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PMID:[The role of nephrologist in treatment of multiple myeloma]. 1857 31

Vorinostat (Zolinza), a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs) associated with monotherapy (n = 341) were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), anorexia (48.1%), and vomiting (32.8%), and Grade 3/4 drug-related AEs included fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.3%), and decreased platelet count (5.3%). The most common drug-related AEs observed with vorinostat in combination therapy (n = 157, most of whom received vorinostat 400 mg qd for 14 days) were nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), vomiting (31.2%), and anorexia (20.4%), with the majority of AEs being Grade 2 or less. In Phase I trials, combinations with vorinostat were generally well tolerated and preliminary evidence of anticancer activity as monotherapy or in combination with other systemic therapies has been observed across a range of malignancies. Ongoing and planned studies will further evaluate the potential of vorinostat in combination therapy, including combinations with radiation, in patients with diverse malignancy types, including non-small-cell lung cancer, glioblastoma multiforme, multiple myeloma, and myelodysplastic syndrome.
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PMID:Vorinostat in solid and hematologic malignancies. 1963 46

Renal failure is a common complication in the course of multiple myeloma (MM). It is being observed in 20-40% of patients at the moment of disease diagnosis and in 10-36% of the cases dialysis treatment is required. Kidney damage is mainly caused by the toxic effect of monoclonal light chains, also known as Bence-Jones proteins produced by the pathological plasma cells. Light chains coaggregate with Tamm-Horsfall glycoprotein leading to casts formation in the distal nephron (cast nephropathy). Additional factors causing renal damage in MM may be dehydration, hypercalcemia, hyperuricemia as well as drug nephrotoxicity. We have described a 49 year-old woman diagnosed with IgA multiple myeloma at IIIB advance stage according to Durie and Salmona classification. The disease course was complicated by renal failure. Myeloma treatment (cyclophosphamide + talidomid + dexamethasone) was initiated simultaneously with hemodialysis therapy. Treatment with this was successful even though disease course was very severe and required longer-term hemodialysotherapy. Complete hematological remission was obtained and after 17 months of renal replacement therapy--hemodialysis treatment was ceased due to improvement of renal function. The presented case confirms the necessity of dialysis therapy initiation in every case of acute renal failure in the course of multiple myeloma--even when symptoms indicates an advanced stage of the disease. Initiation of dialysis therapy allows to initiate and continue the effective multiple myeloma treatment. This is the chance for recovery of renal function to such a level that dialysis treatment could be ceased, even after many months of dialysis therapy.
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PMID:[Withdrawal of maintenance dialysis in a patient with diagnosed multiple myeloma and renal failure as a consequence of effective anti-tumor treatment]. 2138 73

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycaemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium, and magnesium. Whereas diabetes insipidus is a disease of collecting tubules and child mainly presents with dehydration and hypernatremia. Though all the cases published till date were secondary to drugs, myeloma, hematological disorders, etc., we are reporting the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi syndrome. We hypothesized that the NDI may be due to of severe hypokalemia induced tubular dysfunction.
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PMID:Nephrogenic diabetes insipidus with idiopathic Fanconi's syndrome in a child who presented as vitamin D resistant rickets. 2202 6


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