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)

Thalidomide is the drug of choice in the treatment of severe erythema nodosum leprosum (ENL) in men. It has recently been associated with deep venous thrombosis (DVT) when used in treatment of refractory multiple myeloma along with combination chemotherapy. We report a case of DVT in a patient treated for ENL with corticosteroids and thalidomide, and suggest a possible mechanism for the association.
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PMID:A case report of venous thrombosis in a leprosy patient treated with corticosteroid and thalidomide. 1871 41

The study was aimed to investigate the clinical efficacy and adverse reactions of different thalidomide regimens in the treatment of multiple myeloma (MM), and to explore the relationship between efficacy of thalidomide and serum level of TNF-alpha in MM patients. The 85 patients with MM were divided into 5 groups according to different combinations of thalidomide. These 5 groups were following: group with the high dose (HD-T), group with thalidomide+VAD chemotherapy (T-VAD), group with thalidomide+MP chemotherapy (T-MP), group with thalidomide plus dexamethasone (TD), and group with low dose of thalidomide (LD-T). Except 5 groups mentioned above, the group with conventional VAD chemotherapy was served as the control. Clinical effects, adverse reactions, treatment-related mortality were observed. At the same time, serum levels of TNF-alpha in 30 cases of MM treated with thalidomide (15 cases effective and 15 cases ineffective) before and after treatment were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and were compared with the clinical efficacy. The results showed that the efficient rate of HD-T, T-VAD, T-MP, TD, LD-T groups were 25.0%, 80.0%, 71.4%, 33.3%, 27.3% respectively; the efficacy of T-VAD, T-MP groups were significantly higher (p<0.05) than that of other groups and conventional VAD chemotherapy group. The incidence of significant adverse reactions (peripheral neuropathy, fatigue, abdominal distension and constipation, rash, edema, leukocyte and platelet decrease) in 5 groups were 75.0%, 30.0%, 28.6%, 14.3%, 9.1% respectively, no IV grade toxicity and deep vein thrombosis were found. The treatment-related mortality was 0%. At the same time, it was found that the serum levels of TNF-alpha in ineffective group treated with thalidomide were 44.7+/-5.7 pg/ml and 46.3+/-4.0 pg/ml before and after thalidomide treatment, and there was no significant difference (p>0.05). The serum levels of TNF-alpha (27.3+/-6.4) pg/ml in the effective group after treatment was significantly lower than that before treatment (49.2+/-7.3) pg/ml (p<0.05). It is concluded that compared with conventional chemotherapy, thalidomide is a effective drug for treating MM patients. Thalidomide in combination with chemotherapy (T-VAD, T-MP) may be one better therapeutic regimen with high efficiency and milder adverse reactions. Serum level of TNF-alpha is an indicator for finding effects of thalidomide, and plays a role in the pathogenesis of MM.
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PMID:[Efficacy of different thalidomide regimens for patients with multiple myeloma and its relationship with TNF-alpha level]. 1909 34

To obtain approval from the Ministry of Health, Labor and Welfare of Japan, a phase II study was conducted to assess the pharmacokinetics and pharmacodynamics of thalidomide along with its efficacy and safety in Japanese patients with multiple myeloma. Between 2005 and 2006, 42 patients were enrolled, and 37 patients met eligibility criteria. Of the 37 patients, 3 were excluded from efficacy analysis because of short duration of thalidomide administration (<4 weeks). The overall response rate was 35.3% (12/34), including partial response of 14.7% (5/34) and minimal response of 20.6% (7/34). The adverse events observed in high frequency (>40%) were leukopenia, neutropenia, drowsiness, dry mouth, and constipation. Grade 3 neutropenia was observed in nine cases. Peripheral neuropathy and eruption were observed in about one-quarter of the patients. Deep vein thrombosis was not observed. At a single oral dose of thalidomide (100 mg), the C (max) was 1.68 +/- 0.41 microg/ml, T (max) was 4.54 +/- 1.71 h, T (1/2) was 4.86 +/- 0.44 h, and AUC was 15.87 +/- 3.05 microg h/ml. Low-dose thalidomide was an effective and tolerable treatment for Japanese patients with relapsed/refractory myeloma. Leukopenia and neutropenia were the most serious adverse events. The pharmacokinetics was similar to those observed in Caucasian patients.
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PMID:Phase II and pharmacokinetic study of thalidomide in Japanese patients with relapsed/refractory multiple myeloma. 1939 82

(1) Bortezomib prolongs survival in patients with relapsed or refractory multiple myeloma by a few months, but it provokes frequent and sometimes severe adverse effects. Thalidomide is generally used as a last resort; (2) Lenalidomide, a structural analogue of thalidomide, is licensed for the treatment of multiple myeloma, in combination with dexamethasone, after failure of the initial treatment regimen; (3) There are no comparative trials versus bortezomib or thalidomide; (4) Combined analysis of 2 randomised double-blind trials of lenalidomide + dexamethasone versus placebo + dexamethasone in a total of 704 patients showed that adding lenalidomide to dexamethasone slightly increased the one-year survival rate, from 75% to 82%. When this combination was used, the median time to tumour progression was 11 months. In clinical trials, the median time to tumour progression was about 2 years with thalidomide and 8 months with bortezomib; (5) In clinical trials, lenalidomide, like thalidomide, provoked deep venous thrombosis (9% versus 4% with placebo) and pulmonary embolism (4% versus 1%). Lenalidomide, unlike thalidomide, does not appear to cause peripheral neuropathy, but it does provoke cardiac arrhythmia such as atrial fibrillation (18% versus 11% with placebo) and severe haematological disorders, including neutropenia (35% versus 3% with placebo), thrombocytopenia (13% versus 6%) and anaemia (11% versus 6%); (6) The teratogenic effect of lenalidomide has not been adequately documented; (7) Lenalidomide costs about 40% more than bortezomib in France; (8) In patients with relapsed or refractory multiple myeloma there is no evidence that lenalidomide has a more favourable risk-benefit balance than bortezomib or even thalidomide.
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PMID:Lenalidomide: new drug. Myeloma: many questions remain unanswered. 1942 42

After decades of disuse because of its teratogenic effects, thalidomide has had a resurgence of use as a promising therapeutic agent for multiple myeloma. Its mechanism of action involves activation of the immune system, antiangiogenic effects, and inhibition of cytokines. Thalidomide does not interact with the cytochrome oxidase system. It is not significantly metabolized, but it does undergo nonenzymatic hydrolysis in plasma. The resulting products are inactive. Despite the potential adverse effects of peripheral neuropathy, constipation, deep vein thrombosis, somnolence, rash, and orthostatic hypotension, thalidomide is an effective first-line agent for multiple myeloma in combination with dexamethasone or melphalan and prednisone. It has also been studied in the palliative care of patients with cytokine-based syndromes such as anorexia-cachexia syndrome. This review describes its use in oncology, hematology, and palliative care.
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PMID:Palliative oncology: thalidomide. 1984 80

Thalidomide is now recognized as an important agent for multiple myeloma. In this study, we retrospectively analyzed the effect of thalidomide therapy in 52 patients with relapsed/refractory multiple myeloma. Median age was 70 years. Eight patients were treated with thalidomide alone, 36 with dexamethasone, and 8 with chemotherapy. The maintenance dose of thalidomide was 100 mg/day in 42 cases. The probability of overall survival and progression-free survival one year after the start of thalidomide were 76.2% and 70.9%, respectively. Complete or partial response was obtained in 16 patients (31%). The probability of survival was better in patients who obtained a partial or complete response than in non-responders (P=0.04). Adverse effects (CTCAE criteria Grade 3-4) were somnolence (n=3), constipation (n=5), peripheral neuropathy (n=1), deep vein thrombosis (n=1), anemia (n=10), leukocytopenia (n=10), and thrombocytopenia (n=3). The high incidence of cytopenia in this study suggests that the Japanese population tends to display bone marrow suppression after thalidomide therapy. Some patients developed peripheral neuropathy at the early stage of administration and attention was necessary. In conclusion, thalidomide therapy is safe and effective in patients with refractory multiple myeloma.
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PMID:[Retrospective analysis of thalidomide therapy in patients with relapsed/refractory multiple myeloma]. 2037 2

Bortezomib-based regimens have significant activities in multiple myeloma (MM). In this study, we tested the efficacy of a total therapy with a staged approach where newly diagnosed MM patients received vincristine/adriamycin/dexamethsone (VAD). VAD-sensitive patients (> or =75% paraprotein reduction) received autologous hematopoietic stem cell transplantation (auto-HSCT), whereas less VAD-sensitive patients (<75% paraprotein reduction) received bortezomib/thalidomide/dexamethasone (VTD) for further cytoreduction prior to auto-HSCT. On an intention-to-treat analysis, a progressive increase of complete remission (CR) rates was observed, with cumulative CR rates of 48% after HSCT. Seven patients progressed leading to three fatalities, of which two had central nervous system disease. The 3-year overall survival and event-free survival were 75.1% and 48.3%, respectively. Six patients developed oligoclonal reconstitution with new paraproteins. In the absence of anticoagulant prophylaxis, no patients developed deep vein thrombosis. The staged application of VAD+/-VTD/auto-HSCT resulted in an appreciable response rate and promising survivals. Our approach reduced the use of bortezomib without compromising the ultimate CR rate and is of financial significance for less affluent communities.
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PMID:A staged approach with vincristine, adriamycin, and dexamethasone followed by bortezomib, thalidomide, and dexamethasone before autologous hematopoietic stem cell transplantation in the treatment of newly diagnosed multiple myeloma. 2042 73

The use of erythropoietic agents has been associated with an increased risk of venous thromboembolic events (VTEs), especially in patients with underlying malignancies. However, it is not known whether there is an increased risk of VTE associated with granulocyte growth factors. We reviewed 621 patients undergoing PBSC mobilization using granulocyte growth factors, alone or in combination with CY. Patients with a diagnosis of AL amyloidosis (AL: 114; 18%), multiple myeloma (MM: 278; 44%) Hodgkin lymphoma (HL: 20; 3%) or non-Hodgkin lymphoma (NHL: 209; 33%) were included. Symptomatic VTE occurred in six (0.97%) patients: two AL, two MM and two NHL. Of the six patients, two had pulmonary embolism, one developed deep vein thrombosis and three developed symptomatic catheter related thrombosis. Two patients with AL had heparin-induced thrombocytopenia and thrombosis. We found a low incidence of VTE among patients undergoing PBSC mobilization.
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PMID:Low risk of symptomatic venous thromboembolic events during growth factor administration for PBSC mobilization. 2043 22

Bortezomib has proven to be active in patients with multiple myeloma (MM), including elderly patients. The aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with intermediate-dose dexamethasone (Dex) and thalidomide in untreated MM patients aged > or =65 years in a Chinese single center. In this study, 18 patients were treated with bortezomib at 1.3 mg/m(2) IV on Days 1, 4, 8, and 11 and Dex at 20 mg/day IV on Days 1-4 and 8-11 simultaneously. Thalidomide at dose of 100 mg/day was given everyday. The mean number of cycles of bortezomib treatment was 2.06. Three patients (17%) achieved a complete response (CR), four (22%) a very good partial response (VGPR), and nine (50%) a PR, resulting in an overall response rate of 89%. The median time to response was 22 days (range 14-50 days). The duration of response was significantly longer in patients achieving a CR/VGPR with respect to those achieving only a PR (8.5 vs. 4.2 months, P = 0.03). Grade 3-4 toxicities occurring in patients comprised weakness, thrombocytopenia, diarrhea, infection, and neuropathy. Only one patient suffered from deep vein thrombosis. This preliminary experience in Chinese patients indicated that bortezomib-Dex-thalidomide is highly effective in elderly untreated patients with MM, even in patients with poor prognostic features.
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PMID:Bortezomib plus intermediate-dose dexamethasone and thalidomide in elderly untreated patients with multiple myeloma: a Chinese experience. 2057 36

The aim of this Phase II study was to determine the efficacy and safety of combined bortezomib and thalidomide (VT) regime as initial treatment for newly diagnosed patients with multiple myeloma (MM) in China. Thirty-four patients have been enrolled in this study and were planned to receive VT regime up to eight 21-day cycles. Bortezomib (1.3 mg/m(2) ) was given intravenously on days 1, 4, 8, and 11, while oral thalidomide (100 mg/day) was given on days 1 to 21. The primary end point was clinical response; the secondary end point was safety. Among 34 patients enrolled, 26 patients were able to complete the planned eight cycles of therapy. After eight cycles, the overall response rate was 100% (complete response 31%; near-complete response 23%; partial response 42%; minimal response 4%). The best response occurred within the first four cycles in 96% of patients. Adverse events included hematologic (53%), peripheral neuropathy (38%), fatigue (35%), gastrointestinal (45%), and fever (32%). Grade 3 nonhematologic adverse events included four patients (12%) with renal failure associated with tumor lysis syndrome, one patient (3%) with peripheral sensory and motor neuropathy that improved with VT dose reduction, and one patient (3%) with hypotension. One patient (3%) experienced Grade 4 thrombocytopenia. No patient experienced deep venous thrombosis, while 1 patient (3%) died due to acute renal failure. In conclusion, Bortezomib in combination with thalidomide is a very effective regimen for newly diagnosed MM patients and the toxicities are manageable.
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PMID:Bortezomib plus thalidomide for newly diagnosed multiple myeloma in China. 2073 18


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