Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031117 (peripheral neuropathy)
 10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0 mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2) cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.
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PMID:A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. 1546 22

Multiple myeloma (MM), a malignancy of the plasma cells, accounts for an estimated 14% of all newly diagnosed hematologic malignancies. Advances in chemotherapy and stem cell transplantation have improved survival rates, but MM remains incurable. Bortezomib (Velcade, Millennium Pharmaceuticals, Inc., Cambridge, MA), a first-in-class proteasome inhibitor, has been approved for patients with MM who have received at least two prior treatments and have demonstrated disease progression on the most recent one. During clinical trials, most side effects were manageable with standard interventions. The most common toxicities were asthenic conditions (fatigue, malaise, and weakness), gastrointestinal disturbances (nausea, vomiting, diarrhea, and constipation), thrombocytopenia, peripheral neuropathy, pyrexia, and anemia. Supportive therapies and strategies for side-effect management can prevent worsening of these symptoms, thereby avoiding dose reductions and treatment delays. Oncology nurses play a key role in ensuring the proper and safe administration of bortezomib and often are the first to identify the signs of side effects. Patient education about anticipated side effects and close monitoring of patients can lead to symptom management interventions that are essential to patient comfort and safety.
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PMID:Bortezomib, a newly approved proteasome inhibitor for the treatment of multiple myeloma: nursing implications. 1551 81

Bortezomib (PS-341, Velcade) is a novel, first-in-class proteasome inhibitor with antitumor activity against a number of hematologic and nonhematologic malignancies. Based on the results of phase II clinical trials, bortezomib received accelerated US Food and Drug Administration approval on May 13, 2003, for the treatment of multiple myeloma patients whose disease has progressed after they have received at least two prior conventional therapies. The results of phase III studies evaluating bortezomib as first- or second-line therapy, or in combination with other commonly prescribed therapies in multiple myeloma patients, are eagerly awaited. Studies assessing the antitumor effects of bortezomib in other hematologic malignancies and solid tumors are also under way. A thorough understanding of the pharmacology, pharmacodynamics, and pharmacokinetics of this novel compound is essential for appropriate prescribing and monitoring of bortezomib therapy. Bortezomib is rapidly distributed into tissues after administration of a single dose, with an initial plasma distribution half-life of less than 10 minutes, followed by a terminal elimination half-life of more than 40 hours. Maximum proteasome inhibition occurs within 1 hour and recovers close to baseline within 72 to 96 hours after administration. Bortezomib is primarily metabolized by oxidative deboronation to one of two inactive enantiomers that are further processed and eliminated, both renally and in bile. Bortezomib has been shown to be a substrate of several cytochrome P450 isoenzymes using in vitro systems. Adverse effects of bortezomib are generally mild and effectively managed with supportive care. Bortezomib should be administered with caution to patients with preexisting fluid retention and patients with baseline platelet counts of less than 70,000/microL. Dose reductions are recommended for patients experiencing peripheral neuropathy, grade 3 or higher nonhematologic toxicities, or grade 4 hematologic toxicities. Formal drug interaction studies have not been performed, but bortezomib has been administered in combination with a variety of antitumor agents without significant alterations to its pharmacokinetic or pharmacodynamic profile.
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PMID:Pharmacology, pharmacokinetics, and practical applications of bortezomib. 1568 98

Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its toxicity is manageable, and the most frequent adverse effects mainly consist of gastrointestinal symptoms, peripheral neuropathy, neuropatic pain, and thrombocytopenia. Severe liver toxicity has not been previously recognized. A patient with relapsed multiple myeloma who developed bortezomib-induced severe recurrent hepatitis is described. The importance of recognizing this rare potential toxicity is highlighted in order to discontinue this agent if liver adverse reaction is suspected.
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PMID:Bortezomib-induced severe hepatitis in multiple myeloma: a case report. 1573 79

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.
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PMID:A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma. 1610 Apr 50

Proteasome inhibition is a novel approach to treating malignancy, and bortezomib is the first proteasome inhibitor in this class to be approved for clinical use. In preclinical studies, bortezomib caused cell cycle arrest and apoptosis in myeloma and lymphoma cell lines as well as in other neoplastic cell types. Phase I clinical trials established an optimal dosing strategy and demonstrated a manageable toxicity profile. Cyclical thrombocytopenia and peripheral neuropathy, which generally abate after cessation of treatment, are the most clinically significant toxicities. Two phase II trials, SUMMIT and CREST, demonstrated impressive activity with bortezomib 1.3 mg/m2 monotherapy in relapsed and refractory myeloma, with an impressive 35% response rate (complete+partial+minimal responses) in SUMMIT and a 50% response rate in CREST, using the rigorous European Group for Blood and Marrow Transplantation criteria. A recently completed phase III trial showed the significant clinical benefits of bortezomib over high-dose dexamethasone in patients with relapsed myeloma. Results of ongoing trials with bortezomib in the first-line treatment of myeloma have been extremely encouraging and have demonstrated the benefit of using bortezomib as part of an induction regimen prior to stem cell transplantation. Importantly, two clinical trials with bortezomib as monotherapy in refractory non-Hodgkin's lymphoma have shown impressive response rates, particularly in aggressive mantle cell lymphoma.
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PMID:Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies. 1629 74

Despite intensive therapy, multiple myeloma (MM) remains an incurable disease, and novel treatment approaches are therefore needed to improve outcome. Bortezomib is the first proteasome inhibitor to be approved by the U.S. Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products for the treatment of refractory or relapsed MM following the failure of at least two prior lines of therapy. Recently, it also received approval from the FDA for use as a second-line agent. An expert panel of hematologists met at the Ninth Congress of the European Hematology Association to review clinical data and experience in the treatment of MM with bortezomib, including bortezomib-based combination therapy. The conclusions of this expert panel, together with updated clinical data from the American Society of Hematology 46th Annual Meeting, provide a practical update on the use of bortezomib in MM. Bortezomib has demonstrated significant antitumor activity as a single agent in refractory and/or relapsed MM, with a significantly longer survival than with dexamethasone (1-year overall survival rate of 80% vs. 66%) and a 78% longer median time to progression. In combination therapy, patient responses suggest the possibility of chemosensitization and synergy. Furthermore, bortezomib does not appear to have an adverse effect on subsequent stem cell therapy. Bortezomib is well tolerated; most side effects are only mild to moderate and are manageable. Information is given on the practical management of the most common adverse events, including peripheral neuropathy and thrombocytopenia, and the use of bortezomib in renal and hepatic impairment.
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PMID:A practical update on the use of bortezomib in the management of multiple myeloma. 1640 13

Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its frequent adverse effects are manageable, including gastrointestinal symptoms, peripheral neuropathy, and thrombocytopenia. Severe lung toxicity has not previously been reported. Between June 2004 and September 2005, 13 Japanese patients with multiple myeloma were treated with bortezomib in Toranomon Hospital, Juntendo University School of Medicine, and Jichi Medical School. Four of them developed severe pulmonary complications, and 2 died of respiratory failure without progression of underlying disease. To our knowledge, this is the first report on life-threatening pulmonary adverse effects after bortezomib therapy. Previous clinical studies on bortezomib, mostly in the United States and Europe, have shown low incidences of pulmonary adverse effects. Our study suggests that bortezomib can cause serious lung injury, and that its incidence might vary among different ethnicities. Clinicians need to be alert to the possibility.
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PMID:Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma. 1686 61

The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma (MM). Adverse events, including thrombocytopenia and peripheral neuropathy, have affected 30% to 60% of patients overall, and interrupted therapy in 10% to 20%. No prior toxicity data are available for Asian patients who have used bortezomib for MM. We used National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to review the clinical records of patients with an MM diagnosis from 25 centers in Korea. The included patients were treated with bortezomib alone or in combination with other agents, including thalidomide. Ninety-five MM patients were treated. The patients had a median age of 60 years (range, 42-77 years). The median number of previous treatments was 3 (range, 0-10), and 39% of the patients had been treated with 4 or more major classes of agents, including thalidomide (67%), and autologous stem cell transplantation (51%). Regimens included bortezomib only in 38 patients (40%), bortezomib plus dexamethasone in 34 patients (36%), and bortezomib plus a thalidomide-containing regimen in 23 patients (24%). The analysis of patient response to therapy revealed a complete response (CR) or a near-CR in 31 patients (33%) and a partial response in 30 patients (32%), for an objective response rate of 65% in 93 patients. The most common adverse events reported were thrombocytopenia (47%), sensory neuropathy (42%), anemia (31%), and leukopenia (31%). Thirteen patients (14%) stopped therapy because of adverse events (neuropathy, 8; infection, 4; diarrhea, 1). Neuropathy greater than grade 2 was more frequent in patients who received 4 or more prior therapy regimens (17/37) than in those who received 3 or fewer (14/58). In addition, therapy including thalidomide was significantly correlated with neuropathy of grades 1 to 3 (P = .001). We identified 6 therapy-related deaths (6%) within 20 days after the last dose of bortezomib. The causes of death were infection in 3 patients, disease progression in 2 patients, and suicide in 1 patient. The incidences of thrombocytopenia and neurotoxicity were similar; however, gastrointestinal toxicities were relatively low in Korean patients compared with those reported in Western studies. Significant neuropathy was associated with the number of prior regimens and combination with thalidomide. These findings provide useful information for clinicians and patients using bortezomib.
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PMID:A multicenter retrospective analysis of adverse events in Korean patients using bortezomib for multiple myeloma. 1675 29

Bortezomib (Velcade, Millennium) is the first proteasome inhibitor to be used in clinical practice and is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy. Bortezomib inhibits the intracellular degradation of proteins necessary for normal cell cycling and function. This, in turn, results in cell-cycle arrest and apoptosis. Bortezomib has shown significant activity in trials of patients with relapsed or refractory multiple myeloma; approximately one third of patients have shown significant improvement with bortezomib monotherapy in phase II and III clinical trials. Early phase trials are also evaluating bortezomib in combination with other agents used in the treatment of multiple myeloma, including melphalan, prednisone, thalidomide, and lenalidomide. Preliminary data suggest that bortezomib may act synergistically with some agents, and improves response rates. Bortezomib is generally well tolerated, but common side effects include peripheral neuropathy and thrombocytopenia. Studies are underway to explore different dosing strategies as well as ways to maximize patient benefit while reducing toxicity. This review will discuss what is known thus far about the efficacy and safety profile of bortezomib, ways for optimizing treatment with bortezomib, and strategies for managing side effects and enhancing quality of life.
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PMID:Optimizing the efficacy and safety of bortezomib in relapsed multiple myeloma. 1683 Apr 22


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