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)

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

Pseudoachalasia is a rare clinical entity with clinical, radiographic, and manometric features often indistinguishable from achalasia. Primary adenocarcinomas arising at the gastroesophageal junction or a tumor of the distal esophagus are the most frequent causes of pseudoachalasia. Rarely, processes other than esophagogastric cancers including chronic idiopathic intestinal pseudo-obstruction, amyloidosis, sarcoidosis, Chagas' disease, vagotomy, antireflux surgery, pancreatic pseudocysts, von Recklinghausen's neuroinomatosis, gastrointestinal stromal tumor, and other malignancies and rare genetic syndromes, may lead to the development of pseudoachalasia. Secondary achalasia is extremely rare, with less than 100 cases reported in the literature so far. Gastrointestinal manifestations in primary or secondary amyloidosis include abdominal pain, diarrhea, constipation, malabsorption, obstruction, motility disturbance, intestinal infarction, perforation, and hemorrhage; however, gastrointestinal tract involvement is asymptomatic in most instances. We present here a rare case of multiple myeloma initially presenting with dysphagia because of esophageal amyloidosis and manometric findings typical of achalasia.
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PMID:A rare case of multiple myeloma initially presenting with pseudoachalasia. 1920 46

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

We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37-70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n=4), or 25 mg (n=20), orally once daily on day 1 to day 1 every 28 days, with (n=20) or without (n=4) DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n=9), fatigue (n=5) and constipation (n=2). Mild grade I-II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring after lenalidomide showed significant increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells, as well as regulatory T cells (CD4(+), CD25(+), CD127(lo)), supporting an immunomodulating anti-myeloma effect of lenalidomide.
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PMID:Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells. 1958 25

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

Factors that affect the response of multiple myeloma patients to thalidomide were evaluated in 40 patients who were not eligible for chemotherapy (untreated: 14, relapse/refractory: 26). The complete response (CR) rate was 2.5%; partial response (PR) 50.0%; minimal response (MR) 25.0%; no change (NC) 12.5%; and progressive disease 10.0%. The response to thalidomide could be evaluated after four weeks of treatment. Significantly higher responses were associated with untreated patients, patients with combined use of thalidomide plus dexamethasone, and patients with kappa light chain. Patients who responded well to thalidomide showed a significantly higher progression-free survival (PFS) rate. In patients with kappa light chain, PFS and overall survival rates were significantly higher than those with lambda light chain. Frequent adverse reactions were numbness (47.5%), constipation (32.5%), and eruption (30.0%). In patients previously treated with vincristine, numbness occurred in a significantly higher percentage of patients.
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PMID:[Factors affecting the response of thalidomide therapy for patients with multiple myeloma]. 2037 13

In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855.
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PMID:Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. 2081 3

Imexon [AOP99.0001 (4-imino-1,3-diazobicyclo[3. 1. 0]-hexan-2-one)] belongs to a novel class of promising anticancer agents that induce tumor apoptosis through oxidative stress. Clinical experience since the late 1960s has provided initial evidence for a clinical antitumor activity. Our open-label, multicenter phase I clinical trial was designed to further investigate the adverse event (AEs) profile and pharmacokinetics of AOP99.0001 in pretreated myeloma patients and collect initial data on the potential clinical efficacy in this indication. Thirty-six patients with relapsed or refractory myeloma, who had been pretreated with at least two lines of therapy earlier, were included. Imexon was applied intravenously on 5 consecutive days for 2 weeks (d1-5 and d8-12) for a 3-week cycle. The plasma half-life of AOP99.0001 and its active metabolite AOP99.0002 was found to be approximately 1.2 and 2.6 h, respectively. The mean duration of treatment with Imexon was 6.8 weeks in a dose range between 50 and 1000 mg/m without reaching dose-limiting toxicity. Drug-related AEs occurring with a frequency of greater than 10% were fatigue, nausea, constipation, headache, asthenia, anemia, thrombocytopenia, leukopenia and creatinine increase. A total of nine severe adverse events occurred in three patients. No mortality was encountered when patients were on treatment with Imexon. Preliminary antimyeloma efficacy of AOP99.0001 was observed with 1 minimal response, 12 (36%) stable disease responses, and all other evaluable patients had progressive disease. Remarkably, the patient with minimal response also experienced a complete clinical resolution of myeloma-associated polyneuropathy. Overall, Imexon was safe and well tolerated in the dose range investigated. Imexon showed minor clinical activity as a single agent in heavily pretreated myeloma patients. On account of its unique mechanism of action, favorable toxicity profile, initial clinical evidence for antimyeloma activity, and its known synergistic activity in combination with approved agents for myeloma treatment, AOP99.0001 is recommended for future clinical studies in combination regimens in multiple myeloma.
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PMID:Combined phase I/II study of imexon (AOP99.0001) for treatment of relapsed or refractory multiple myeloma. 2057 55

The study was aimed to evaluate the adverse effects of PAD (bortezomib + adriamycin + dexamethasone) and VAD (vincristine + adriamycin + dexamethasone) as chemotherapy regimens in multiple myeloma patients. 27 and 30 patients with multiple myeloma (MM) were enrolled in PAD and VAD groups respectively. MM patients accepted 3 - 5 cycles of VAD or PAD regimens. The type, degree and occurrence time of adverse reactions during the treatment were observed. The results showed that the rash was found in two patients only in PAD group, leucocytopenia, thrombocytopenia, peripheral neuropathy, infection, fatigue, nausea, constipation, and adverse effects of cortex hormone (hypertension, glycemia, hypokalemia, hyponatremia and acne) were found in the both two groups. The thrombosis was not observed in both two groups during treatment. Although statistical analysis indicated that only the incidence of thrombocytopenia was higher in PAD group than in VAD group with statistical difference but the incidence of leucocytopenia, peripheral neuropathy and infection in PAD group were higher than those in VAD group. Rash, constipation, peripheral neuropathy could be found in the first course of chemotherapy, while the others mostly emerged after 3 courses of treatment. The main reasons for the patients who's treatment was stopped include infection and intolerable peripheral neuropathy. Although peripheral neuropathy could be found in the two groups, but the chemotherapy was stopped only in 2 patients of PAD group after 3 cycles of treatment. It is concluded that compared with conventional VAD chemotherapy, PAD may improve therapeutic effect, but it may bring more severe toxicities to the patients with multiple myeloma.
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PMID:[Adverse effects of PAD and VAD regimens in multiple myeloma patients]. 2072 22


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