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)

The aim of this study was to assess the side effects and the efficacy of thalidomide alone or in combination with dexamethasone in relapsed multiple myeloma (MM) and to evaluate possible predictive factors for response rate and survival. Twenty-nine pretreated patients were enrolled, including 13 patients with a relapse after high-dose chemotherapy. The median number of relapses was 3 (range: 1-7). Twenty-two patients received thalidomide in combination with dexamethasone and seven patients thalidomide alone. The dosage of thalidomide was 400 mg/day and the dosage of dexamethasone 20 mg/m2 daily for 4 consecutive days every 3 weeks. Cycles of dexamethasone were given until maximal decline of myeloma protein was achieved, whereas therapy with thalidomide was maintained until disease progression. Responses occurred in 62% of patients, including 5 (17%) complete remissions and 13 (45%) partial remissions. The median event-free survival (EFS) was 7.2 months and the median overall survival (OS) 26.1 months. In multivariate analysis, pretreatment serum levels of soluble interleukin-2 receptor (sIL-2R) were a significant prognostic factor for EFS, and those of beta2-microglobulin (beta2M) and sIL-2R for OS. Serum levels of sIL-2R significantly increased after 3 weeks of treatment in 89% of patients, possibly representing lymphocyte activation induced by thalidomide. Two patients died of septic complications within 3 months after starting treatment with thalidomide and dexamethasone and one patient of herpes encephalitis after 26 months of treatment with thalidomide alone. Also, one case of pneumonia and one case of deep venous thrombosis of the lower limb occurred. Other side effects were somnolence, peripheral neuropathy, and bradycardia occurring in 35, 55, 38 and 55% of patients, respectively. The combination of thalidomide and dexamethasone is an effective therapy in heavily pretreated myeloma patients with a high response rate and acceptable toxicities. A powerful predictive factor both for EFS and OS was the pretreatment serum level of sIL-2R.
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PMID:Thalidomide in combination with dexamethasone for pretreated patients with multiple myeloma: serum level of soluble interleukin-2 receptor as a predictive factor for response rate and for survival. 1574 24

Pregabalin is an anticonvulsant drug that is under review for use in Canada. It was recently approved in the US and Europe for the treatment of adults with peripheral neuropathic pain (NeP). In most short-term randomized controlled trials (RCTs) of pregabalin in patients with diabetic peripheral neuropathy (DPN) and or post-herpetic neuralgia (PHN), there were early and significant decreases in mean pain scores. The number of subjects with > 50% reduction in pain score was increased when pregabalin was compared to placebo. The most common adverse effects were dizziness and sleepiness. Withdrawal due to adverse events was also more frequent with pregabalin than with placebo. While pregabalin appears to be an effective treatment for NeP, there is no evidence that it offers advantages over treatments being used in Canada.
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PMID:Pregabalin for peripheral neuropathic pain. 1580 48

Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.
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PMID:Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. 1591 Nov 52

Thalidomide has several mechanisms of action: a hypnosedative effect, several immuno-modulatory properties and an anti-angiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (such as erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions. Several side effects are associated with thalidomide: teratogenicity, peripheral neuropathy and deep venous thrombosis; some are minor, such as somnolence or abdominal pain and endocrinologic disturbances. Use of thalidomide is strictly controlled with close adherence to a birth control program and close monitoring for early development of peripheral neuropathy.
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PMID:[Thalidomide: new indications for an old drug]. 1593 72

Thalidomide represents a recent and innovative therapeutic approach in multiple myeloma. Main toxicity usually consists in somnolence, constipation, peripheral neuropathy and deep vein thrombosis, but, unlike alkylating agents, thalidomide is reported to rarely induce severe hematologic toxicity. The majority of patients developing neutropenia are heavily pretreated with three or more lines of chemotherapy. Here, we report, for the first time, clinical and laboratory data of a 66-year-old female patient with multiple myeloma at diagnosis who, after 4 weeks of thalidomide treatment, developed a grade 4 WHO neutropenia with septicemia. A brief review of the literature and suggestions for possible predictive factors of this toxicity are made.
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PMID:Low-dose thalidomide-induced agranulocytosis in a multiple myeloma patient treated at diagnosis. 1626 90

Conventional IV chemotherapy regimens used for induction chemotherapy or salvage therapy in the treatment of multiple myeloma (MM) are cumbersome, with a negative impact on patient quality of life. A number of new oral drugs, including immunomodulatory agents such as thalidomide and lenalidomide, have demonstrated potent antimyeloma activity in relapsed and refractory as well as newly diagnosed MM. Clinically, response rates of 56%-72% have been reported with the combination of thalidomide and dexamethasone in patients with newly diagnosed disease; however, the combination is associated with a higher incidence of side effects, including constipation, somnolence, peripheral neuropathy, and thromboembolic complications. In contrast, preliminary safety and efficacy data from clinical studies of lenalidomide show promise. Response rates as high as 83% have been reported in patients with newly diagnosed MM, and the most common adverse event is manageable myelosuppression, which is reversible with dose reduction. Lenalidomide has different toxicities than thalidomide, exhibiting greater myelosuppression but virtually no constipation, somnolence, or peripheral neuropathy. Oncology nurses play a key role in monitoring patients for side effects and pain control and educating them about emerging treatment options. This article reviews the nursing experience with oral agents in the treatment of MM.
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PMID:Advances in oral therapy in the treatment of multiple myeloma. 1692 5

Thalidomide has several mechanisms of action: several immuno-modulatory properties, an anti-angiogenic action and a hypnosedative effect. Thalidomide has been used in several cutaneous inflammatory disorders (such as erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions. Several side effects are associated with thalidomide; some are major: teratogenicity, peripheral neuropathy and deep venous thrombosis; some are minor, such as somnolence or abdominal pain and endocrinologic disturbances. Use of thalidomide is strictly controlled with close adherence to a birth control program and close monitoring for early development of peripheral neuropathy.
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PMID:[The revival of thalidomide: an old drug with new indications]. 1727 97

Thalidomide monotherapy in relapsed/refractory multiple myeloma (MM) has a response rate of 30%. The combination of thalidomide with dexamethasone (Thal/Dex) is expected to improve responses, but it is unknown if the combination increases the rate of adverse events. Here, we conducted a systematic review of studies evaluating Thal/Dex in relapsed/refractory MM. Twelve studies were included, comprising 451 patients. The response rate (CR and PR) was 46% (95% CI 42-51%). Therapy-related toxicity was comparable to thalidomide monotherapy and included somnolence (26%, 95% CI 22-31%), constipation (37%, 95% CI 32-42%) and peripheral neuropathy (27%, 95% CI 23-32%). Only venous thromboembolism appeared to occur more often with Thal/Dex (5%, 95% CI 3-8%). Thus, using Thal/Dex results in an improved response rate in relapsed/refractory MM, with a toxicity rate comparable to thalidomide monotherapy.
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PMID:A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. 1863 31

Reports on the use of thalidomide in the last 20 years have described favorable responses in a variety of inflammatory conditions. We have performed an open trial to begin to assess further its efficacy in rheumatoid arthritis (RA). During a 3-year-period, 31 patients with chronic active RA were enrolled into a 4-month open trial using thalidomide, to assess its efficacy and safety. Of these patients, 21 began the study taking 300 mg/day and the other 10 patients began at lesser doses that were increased gradually. Patients were evaluated at least 7 times during the 4-month study. Of the 31 patients, 17 (55%) withdrew from the study over the course of 12 weeks because of adverse events and no benefit was seen in any of these patients with a mean dose of 177 mg/day. There were 14 patients taking thalidomide for 4 months, and 4 of the 14 (29%) responded to therapy, satisfying at least 4 of the 6 Paulus criteria; 6 of 14 (43%) partially responded to therapy, satisfying 3 of the 6 Paulus criteria; and 4 of 14 (29%) did not respond, with each group taking average dosages, respectively, of 304 mg/day, 264 mg/day, and 303 mg/day. Of the 14 patients completing the 4-month study, 9 patients consented to participate in an extended trial of thalidomide treatment for at least 4 more months. Patients showing partial benefit within the first 4 months are more likely to show definite benefit later on.This study did not confirm the level of effect previously reported with thalidomide. However, some patients with previously refractory RA did improve. Although we had no comparison group, we believe that, as an investigational therapy, thalidomide should be considered in patients with RA for whom other conventional treatment approaches have failed. Thalidomide should be administered initially at 50 mg/hs for 1-2 weeks and then increased by 50 mg every 1-2 weeks as tolerated. The major obstacle to short term use of thalidomide is drowsiness and the major adverse effect to long term use is peripheral neuropathy.
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PMID:Open trial of thalidomide in the treatment of rheumatoid arthritis. 1907 6

After 1990's, the development of new generation anti-cancer agents produced encouraging improvement of prognosis in inoperable or relapsed stomach cancer and colorectal cancer. However, non-hematological toxicity, such as peripheral neuropathies, become a new dose-limiting toxicity. In several new generation drugs, measures for controlling peripheral neuropathy had not been established besides dose modification or schedule modification. We tried to control the peripheral neuropathy induced by anti-cancer agents with the assistance of an adjuvant analgesics ladder. A total of 18 digestive cancer patients who presented with peripheral neuropathy of grade 1 or more(NCI-CTCAE ver 3.0), in the chemotherapy including Taxol or Oxaliplatin, were enrolled. The first stage of the adjuvant analgesics ladder was set as the antidepressant(amoxapin), the second stage was anticonvulsive drugs(valproic acid or clonazepam) and the third stage was antiarrhythmic drug(mexiletine). In each stage, if the drug turned out to be ineffective after two / weeks follow-up, it shifted to the next stage. The response rate of each step was 61.1%(11/18)of the first stage, 50.0%(5/10)of the 2nd stage, 50.0%(2/4)of the 3rd stage, and the overall response rate was 77.8%. The discontinuance of cancer treatment by peripheral neuropathy was observed only in 1 patient 5.5%(1/18)in the Taxol administered group. The toxicity profile was skin eruption and drowsiness, but the skin eruption was observed only in 1 patient at the 3rd stage and the drowsiness in 2 patients at the 2nd stage. It appears that the method to control the peripheral neuropathy induced by anti-cancer agents with the assistance of adjuvant analgesics ladder was effective and safe, but a large-scale clinical trial was warranted.
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PMID:[Evaluation of efficacy and safety of adjuvant analgesics for peripheral neuropathy induced by cancer chemotherapy in digestive cancer patients-a pilot study]. 1915 68


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