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, administered as a sedative and antiemetic decades ago, was considered responsible for numerous devastating cases of birth defects and consequently was banned from markets worldwide. However, the drug remarkably has resurfaced with promise of immunomodulatory benefit in a wide array of immunologic disorders for which available treatments were limited. It is approved by the Food and Drug Administration for erythema nodosum leprosum (ENL). Although the relative paucity of leprosy and ENL worldwide may perceivably limit interest in and knowledge about thalidomide, increasing numbers of new and potential uses expand its applicability widely beyond ENL. Thalidomide, an inhibitor of tumor necrosis factor a, is the best known agent for short-term treatment of ENL skin manifestations, as well as postremission maintenance therapy to prevent recurrence. For this indication, it is effective as monotherapy and as part of combination therapy with corticosteroids. Studies of thalidomide in chronic graft-versus-host disease showed benefit in children and adults as treatment, but not as prophylaxis. The agent has been administered successfully for treatment of cachexia related to cancer, tuberculosis, and human immunodeficiency virus infection, although evidence of efficacy is inconclusive. Thalidomide monotherapy effectively induced objective response in trials in patients with both newly diagnosed and advanced or refractory multiple myeloma. Combination therapy with thalidomide and corticosteroids was also effective in these patients, as well as in treatment of aphthous and genital ulcers. Limited evidence supports the drug's benefit in treatment of Kaposi's sarcoma. Other thalidomide applications include Crohn's disease, rheumatoid arthritis, and multiple sclerosis. Somnolence, constipation, and rash were the most frequently cited adverse effects in studies, but thalidomide-induced neuropathy and idiopathic thromboembolism were critical causes for drug discontinuation. Thalidomide is still contraindicated in pregnant women, women of childbearing age, and sexually active men not using contraception. Clinicians should be conversant with thalidomide in ENL (its primary application) in the natural course of leprosy, as well as in the agent's other applications.
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PMID:Thalidomide for erythema nodosum leprosum and other applications. 1268 Apr 78

Twelve patients with Waldenstrom's macroglobulinemia (WM) underwent treatment with the nonmyelosuppressive combination regimen BLT-D: clarithomycin (Biaxin [BXN], Abbott Laboratories, Abbott Park, IL) 500 mg orally twice daily, low-dose thalidomide (THAL) 50 mg orally escalated to 200 mg daily, and dexamethasone (DXM) 40 mg orally once weekly all with modification for toxicity. Omeprazole (correction of omepraxole) 20 mgm orally twice daily for 2 days with the DXM, and enteric-coated aspirin 81 mg orally daily were also administered. Twelve patients have been evaluated. All had previously received at least one purine analogue or alkylating agent. Five had a reduction in either leukocytes and/or platelets prior to treatment, of which three were disease-related. Median age was 62 years. All patients received a minimum of 6 weeks of therapy. Of the 12 patients, 10 had a significant response (83%) consisting of three near complete, three major, four partial, and two minor responses. Four of five had restoration of reduced blood counts. Two with minor responses did not receive sufficient dose escalation due to toxicity. Median time on therapy was 7 months (range, 3 to 28 months). Patients were removed from therapy primarily due to neurotoxicity. Drug resistance occurred in three patients, with one transformation to large cell lymphoma. Toxicity was as follows: gastrointestinal (primarily constipation), 42%; neurological, 100%; endocrine, 42%, and thrombotic, 8%. Most toxicities were World Health Organization (WHO) grade 1 or 2; however, neurological toxicity was more prominent and severe in WM patients than in myeloma. BLT-D is effective in WM. Because of its toxicity, predominantly neurological, BLT-D may best serve as an induction regimen or to "rescue" patients with refractory disease or disease-related low counts.
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PMID:Treatment of Waldenstrom's macroglobulinemia with clarithromycin, low-dose thalidomide, and dexamethasone. 1272 Jan 51

Experimental studies have demonstrated that thalidomide (Thal), a drug developed as a sedative, has antitumoural properties. The possible antitumour mechanisms of action involve: inhibition of angiogenesis, cytokine-mediated pathways, modulation of adhesion molecules, inhibition of cyclooxygenase-2 and stimulation of immuno response. Therefore, Thal is under clinical evaluation in oncology. This paper provides an overview of the data currently available in literature regarding, in terms of activity and toxicity, the use of Thal in cancer patients. Multiple myeloma is so far the most responsive malignancy. A moderate activity has been documented in certain solid tumours: glioblastoma multiforme, renal cell carcinoma and malignant melanoma. Tolerability is generally satisfactory with peripheral neuropathy being the most relevant dose-dependent toxicity. The more frequent, but moderate side effects are: somnolence, constipation, dizziness and fatigue. More studies are needed to properly evaluate the anticancer activity of Thal alone or in combination with other anticancer treatments. Preliminary studies suggest promising results of Thal in combinations with corticosteroids and cytotoxic drugs as front-line therapy of multiple myeloma. Regarding therapy of solid tumours in the adult, combination with chemotherapy, radiation therapy and molecular-targeting compounds are under investigation.
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PMID:Thalidomide: a new anticancer drug? 1283 55

A 64-year-old Japanese man suffering from IgD lambda myeloma and renal failure requiring chronic hemodialysis was treated with thalidomide. Serum IgD concentration was 4,050 mg/dl and myeloma cells constituted 95.6% of nucleated cells in bone marrow at the start of treatment. These parameters improved markedly to 1,590 mg/dl and 22.0%, respectively, in the 4 months immediately prior to his death due to pneumonia. Thalidomide caused peripheral neuropathy and constipation at a dose of 100 mg daily in the first week of treatment, but adverse effects resolved upon dose reduction. Thalidomide represents a valid therapeutic option for some myeloma patients receiving hemodialysis.
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PMID:Thalidomide treatment for immunoglobulin D multiple myeloma in a patient on chronic hemodialysis. 1604 13

Thalidomide as a single agent (200-400 mg/day) was administered in fourteen cases of refractory myeloma, from March 2001 till February 2002. The median age was 71 years (range 58 to 85 years), and the efficacy of thalidomide was observed in cases receiving treatment for at least three consecutive months. Response was evaluated in February 2002, according to the criteria for assessment of response described by Kakimoto et al. At the time of evaluation, two cases were in the PR2 state, one in PR3, two were stable, and three were PD. Evaluation of the response was not possible in six cases in whom treatment had to be discontinued due to intolerable side effects. The response to thalidomide was variable, with some cases responding well even to a low dose (200 mg/day) while a few others showed an early relapse due to the refractory nature of the disease in its response to the drug. The efficacy of treatment seemed to be correlated with the maturation pattern of myeloma cells. Side effects included neurological complications like somnolence, physiological symptoms such as constipation and so on, etc but all were relieved with symptomatic treatment. The drug was well tolerated in geriatric patients. Neutropenia was a dose limiting factor with half of the cases (7/14) presenting with severe neutropenia (grade 3-4), but a response was observed in all of them on administration of G-CSF. Thromboembolism occurred in two cases, the cause of which is not clear. These results suggest that thalidomide is a well tolerated drug and can be considered as a mainstay in the therapy of refractory myeloma.
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PMID:[Single-agent thalidomide for advanced and refractory multiple myeloma]. 1288 14

Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m2 i.v. over 3 h q 12 h x 6, d 1-3) with pulsed dexamethasone (20 mg/m2/d p.o., d 1-4, 9-12, 17-20) and once daily thalidomide at individually escalating doses (100-400 mg/d) depending on tolerability (HyperCDT). Responding patients were maintained on daily thalidomide and monthly dexamethasone pulses. Complete, partial and minor response rates were 4%, 68% and 12% respectively; overall response rate was 84% (efficacy analysis). Median event-free and overall survival was 11 and 19 months respectively. During at least one treatment cycle, 67% of patients experienced grade 4 neutropenia resulting in 17% grade 3 and 9% grade 4 infections. Side-effects, presumably related to thalidomide, included neuropathy (40% grade 2, 16% grade 3), constipation (17%), oedema (5%), bradycardia (5%), skin reactions (3%), cerebrovascular events (5%) and deep vein thromboses (8%). Thromboses were not related to known thrombophilic risk factors. Four patients with prior myeloma therapy > 50 months developed myelodysplastic syndrome or secondary acute myeloid leukaemia 2-4 months after study entry. HyperCDT is a highly active and reasonably well-tolerated salvage regimen in advanced or refractory multiple myeloma.
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PMID:Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. 1289 16

Thalidomide, an agent with antiangiogenic and immunomodulatory properties, is therapeutically effective in multiple myeloma, leprosy, and autoimmune diseases. The most common clinical toxicities of thalidomide are constipation, neuropathy, fatigue, sedation, rash, tremor, and edema. We here describe for the first time a patient who developed leukocytoclastic vasculitis during therapy with thalidomide. Of the 260 patients treated with thalidomide in our institution, this is the first patient who developed autoimmune disease. We conclude that patients with malignant disorders who are treated with thalidomide should be carefully monitored for the development of autoimmune disorders. Whether autoimmune phenomena also occur during treatment with new drugs such as PS-341 or potent immunomodulatory agents remains to be evaluated.
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PMID:Development of leukocytoclastic vasculitis in a patient with multiple myeloma during treatment with thalidomide. 1462 89

We evaluate the efficacy of the oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 71 refractory/relapsed multiple myeloma patients, including a prognostic analysis to predict both response and survival. Patients received thalidomide at escalating doses (200-800 mg/day), daily cyclophosphamide (50 mg/day) and pulsed dexamethasone (40 mg/day, 4 days every 3 weeks). On an intention-to-treat basis and using the EBMT response criteria, 2% patients reached complete response (CR), 55% partial response (PR) and 26% minor response (MR) yielding a total response (CR+PR+MR) rate of 83% after 3 months of therapy. After 6 months of therapy, responses were maintained including a 10% CR. The 2-year progression free and overall survival were 57 and 66%, respectively. A favorable response was associated with beta2 microglobulin < or =4 mg/dl, platelets >80 x 10(9)/l and nonrefractory disease. Regarding survival, low beta2 microglobulin (< or =4 mg/dl), age (< or =65 years) and absence of extramedullary myelomatous lesion were associated with a longer survival. Major adverse effects included constipation (24%), somnolence (18%), fatigue (17%) and infection (13%). Only 7% of patients developed a thrombo-embolic event. ThaCyDex is an oral regimen that induces a high response rate and long remissions, particularly in relapsing patients with beta2 microglobulin < or =4 mg/dl and < or =65 years.
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PMID:The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. 1497 8

Treatments effective against multiple myeloma may be useful in primary systemic amyloidosis (AL). Thalidomide is active in myeloma. Results of the first 12 patients enrolled on a phase II trial of thalidomide for AL are presented. Progressive edema, cognitive difficulties, and constipation occurred in approximately 75%; dyspnea, dizziness and rash in 50%. Five developed progressive renal insufficiency. Deep venous thrombosis and syncope each occurred in two. Median time on the study was 72 days, range was 25 to 333 days. All 12 have withdrawn from the study (side-effects, 6; progression, 4; and death, 2 patients). AL patients do not tolerate high dose thalidomide.
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PMID:Poor tolerance to high doses of thalidomide in patients with primary systemic amyloidosis. 1498 85

Based on the activity of single-agent thalidomide demonstrated in relapsed or refractory multiple myeloma, investigators have evaluated the role of this agent in the treatment of earlier stage disease. Two key phase II trials of thalidomide plus dexamethasone in patients with previously untreated symptomatic multiple myeloma have yielded overall response rates of 64% to 73%. Comparable response rates, reduced toxicity, and increased patient convenience with oral administration suggest it may offer an alternative to standard infusional chemotherapies, such as vincristine/doxorubicin/dexamethasone (VAD), before stem cell mobilization and high-dose chemotherapy in patients with active disease; further study is warranted. Two key phase II trials of single-agent thalidomide in patients with smoldering/indolent (asymptomatic) disease have yielded overall response rates of approximately 35%, and further study of thalidomide in this setting is also indicated. The primary toxicities of thalidomide-based therapy are neuropathy, sedation/fatigue, constipation, and rash. Studies of thalidomide in combination with dexamethasone suggest toxicities of both agents may be increased due to the synergy of these agents. Phase III trials of thalidomide in newly diagnosed symptomatic multiple myeloma or smoldering/indolent disease are ongoing.
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PMID:Thalidomide in newly diagnosed multiple myeloma and overview of experience in smoldering/indolent disease. 1501 92


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