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Thalidomide Therapy (thalidomide + therapy)
Selected AbstractsSyncope and sinus bradycardia from combined use of thalidomide and , -blocker,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2008Takashi Yamaguchi MD Abstract We present a case of a 76-year-old Japanese man with hypertension and multiple myeloma (MM) presented with syncope and sinus bradycardia. Thalidomide therapy for MM was added to longstanding atenolol therapy one month prior to presentation. His heart rate (HR) was around 70 beats per minute (bpm) before addition of Thalidomide. His HR on presentation was less than 30,bpm. He was treated with intravenous atropine followed by temporary pacemaker and taken off atenolol. His HR returned to around 70,bpm few days after discontinuation of atenolol, even though he was still taking thalidomide, permitting outpatient management without a pacemaker. Both thalidomide and atenolol have been reported to cause bradycardia. Neither agent caused bradycardia when used alone in this patient, but simultaneous use caused symptomatic bradycardia. As thalidomide is prescribed more frequently, clinicians should be aware of the possibility of drug-induced sinus bradycardia due to the interaction of thalidomide and , -blockers. Copyright © 2008 John Wiley & Sons, Ltd. [source] Thalidomide therapy in adult patients with myelodysplastic syndromeCANCER, Issue 4 2006A North Central Cancer Treatment Group phase II trial Abstract BACKGROUND. Thalidomide has shown promise for the treatment of patients with myelodysplastic syndrome. The current prospective multicenter study examined the efficacy and toxicity of thalidomide in adult patients with myelodysplastic syndrome. METHODS. Using the International Prognostic Scoring System (IPSS), patients were stratified into 2 groups: favorable (IPSS score, 0,1.0) or unfavorable (IPSS score, 1.5,3.5). Seventy-two patients (42 of whom were favorable and 30 of whom were unfavorable) received a starting dose of oral thalidomide of 200 mg daily. The dose was increased by 50 mg per week to a targeted maximum daily dose of 1000 mg. RESULTS. According to the International Working Group response criteria for myelodysplastic syndrome, 1 patient in the unfavorable group achieved a partial remission with a complete cytogenetic response. Overall, 2 patients (5%) in the favorable group and 4 patients (14%) in the unfavorable group experienced either a hematologic improvement or a partial response. The most frequent Grade 3 or 4 (grading was based on the National Cancer Institute's Common Toxicity Criteria [version 2.0]) nonhematologic adverse events were fatigue (24%), infection (19%), neuropathy (13%), dyspnea (8%), and constipation (7%). CONCLUSIONS. Thalidomide alone, at the schedule and dose levels used in the current study, is not a safe and viable therapeutic option for patients with myelodysplastic syndrome. Limited efficacy and increased toxicity were observed in the current Phase II trial. Cancer 2006. © 2006 American Cancer Society. [source] Thalidomide for the treatment of multiple myelomaCONGENITAL ANOMALIES, Issue 3 2004Yutaka Hattori ABSTRACT Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. It is known that thalidomide monotherapy is effective in one-third of refractory cases, and in combination with glucocorticoids and/or antineoplastic drugs, thalidomide provides a response rate of more than 50%. Thus, thalidomide therapy is considered a standard approach for the treatment of relapsed and refractory myeloma. The exact mechanism of the antimyeloma effect of thalidomide is not yet clearly understood. Anti-angiogenic effects, direct activity in tumor cells such as the induction of apoptosis or G1 arrest of the cell cycle, the inhibition of growth factor production, the regulation of interactions between tumor and stromal cells, and the modulation of tumor immunity have been considered as possible mechanisms. In addition to its teratogenicity, the adverse effects of thalidomide have been general symptoms such as somnolence and headache, peripheral neuropathy, constipation, skin rash, and other symptoms. Although these adverse effects are generally reversible and mild, grade 3 and 4 toxicities such as peripheral neuropathy, deep venous thrombosis, neutropenia, and toxic dermal necrosis have occasionally been reported. The application of thalidomide therapy in patients with multiple myeloma is being broadened to include not only cases of refractory myeloma, but also previously untreated cases, as well as for maintenance therapy after hematopoietic stem cell transplantation and for the treatment of other hematological diseases. The safe use of this drug will depend on the establishment of diagnostic and treatment guidelines. In addition, the establishment of a nation-wide regulation system is urgently needed in Japan. [source] Thalidomide-associated neuropathy in multiple myelomaJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004S Morino Thalidomide is a neurotoxic immunomodulating agent currently used in Multiple Myeloma (MM). We prospectively evaluated the frequency and characteristics of peripheral neuropathy in a continuous series of 25 patients (13 M, 12 F; age 38,60, median 55 yrs) treated with thalidomide for MM. Patients underwent a neurological and neurophysiological evaluation before starting thalidomide therapy and monthly throughout duration of treatment. Sixteen patients (5 M, 11 F) developed neurophysiological characteristics of axonal sensitive damage and/or clinical peripheral neuropathy with distal sensory symptoms; treatment duration ranged between 95 and 572 days (median 298) in patients with neuropathy, and 49,264 days (median 162) in patients without neuropathy; the total amount of thalidomide taken ranged between 26 and 169 g (median 83 g) for patients with neuropathy and 13,170 g (median 51 g) for those without. In four patients, ENG alterations appeared before clinical symptoms, while in two patients they were not followed by clinical symptoms. In the remaining three patients, clinical symptoms preceded neurophysiological alterations. Age at onset of MM, disease duration before thalidomide therapy was started, total dose, duration of therapy and previous treatments were not correlated with neuropathy (multivariate logistic regression analysis). Female gender was a risk factor for developing neuropathy (OR 7.7). [source] Extramedullary progression of multiple myeloma under thalidomide therapy despite concomitant response of medullary diseaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2008Anna Candoni No abstract is available for this article. [source] Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapyCANCER, Issue 7 2008Pieter Sonneveld MD Abstract BACKGROUND Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current analysis, they determined 1) the efficacy of PLD plus bortezomib versus bortezomib alone in patients with MM who had failed on prior thalidomide/lenalidomide (immunomodulatory drug [IMiD]) treatment and 2) the efficacy and safety profile of PLD plus bortezomib in IMiD-exposed and IMiD-naive patients. METHODS This prespecified analysis included 646 patients who were randomized to receive either PLD with bortezomib (n = 324; 194 IMiD-naive patients and 130 IMiD-exposed patients) or bortezomib alone (n = 322; 184 IMiD-naive patients and 138 IMiD-exposed patients). The primary efficacy endpoint was TTP, and secondary endpoints included overall survival, response rate, and safety. RESULTS The median TTP was significantly longer with PLD plus bortezomib compared with bortezomib alone in IMiD-exposed patients (270 days vs 205 days). No statistical difference was noted with respect to TTP between IMiD-naive (295 days) versus IMiD-exposed (270 days) subgroups who received PLD plus bortezomib. A sustained trend favoring combination therapy was observed in analyses of overall survival. In patients who achieved a response, the response duration was comparable for IMiD-naive patients and IMiD-exposed patients in the combination treatment group and lasted a median of 310 days and 319 days, respectively. The incidence of grade 3/4 adverse events was similar with PLD plus bortezomib regardless of prior IMiD exposure. CONCLUSIONS A significantly prolonged TTP was observed with combined PLD plus bortezomib combination therapy compared with bortezomib alone despite prior IMiD exposure. For the combination treatment arm in the IMiD-naive and IMiD-exposed subgroups, TTP was comparable. Similarly, the safety profile of the PLD plus bortezomib combination was unaltered by prior IMiD exposure. Cancer 2008. © 2008 American Cancer Society. [source] | ||||||||||