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At least 865 records · Page 48Linked to original sources
PubMed1997

Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients.

We review the efficacy, tolerability and safety of low-dose thalidomide in the treatment of refractory disfiguring rash in 16 patients with cutaneous manifestations of lupus. Rashes, which included discoid lupus erythematosus (DLE), subacute cutaneous lupus (SCLE), photosensitive malar rash and non-specific chronic erythema, were diagnosed on clinical grounds, supported by skin biopsy in 11/16 patients. Using starting doses of 50-100 mg/day, 7/16 (44%) patients gained complete or near-complete remission of skin disease and 6/16 (37%) partial remission. Three out of 16 patients failed to respond. Maximum benefit was achieved within 16 weeks in all patients. Doses of 25-50 mg/day were effective in maintaining response. Rapid relapse occurred in 6/8 (75%) patients following drug withdrawal, but the response to thalidomide in those requiring repeat courses appeared to be maintained. There was no detectable improvement in systemic disease. One patient developed symptoms of mild peripheral neuropathy which resolved on drug withdrawal. Our experience suggests that thalidomide is effective in the treatment of severe skin manifestations of lupus refractory to other treatment and can be used safely in specialist rheumatological practice.

Adult↗
PubMed2002

A tale of two experts: thalidomide and political engagement in the United States and West Germany.

The physicians, Widukind Lenz and Frances Kelsey, played crucial roles in the thalidomide drama of the early 1960s. Widespread use of the drug in West Germany was only halted when the paediatrician, Lenz, publicized its association with the birth of nearly 4,000 children exhibiting abnormal limb growth. Few cases were reported in the United States because Kelsey, a medical officer at the US Food and Drug Administration, repeatedly delayed thalidomide's marketing approval. Experts in both countries were expected to demonstrate publicly the professional 'objectivity' of medicine and the institutional 'disinterestedness' of regulatory bodies. These norms were invoked both by industry representatives seeking to undermine the two experts and by critics desiring stronger regulatory controls. Comparing Lenz and Kelsey demonstrates how institutional structures shape an expert's social and scientific roles. While the United States provided important protection from external pressure for Kelsey through her regulatory position at the FDA, Lenz was open to sharp criticism, especially when giving expert testimony during a lengthy court trial. The degree of exposure to politically motivated attacks differed for these two experts; they nevertheless faced similar threats to their professional credibility and personal integrity when they publicized links between thalidomide and birth defects.

Abnormalities, Drug-Induced↗
PubMed2001

Thalidomide and its dermatologic uses.

This article reviews how the drug thalidomide can be used for various dermatologic disorders. Also included is a short discussion of the chemistry and physiologic mechanisms of thalidomide. Thalidomide, now available again in the United States, is another drug that can be considered by dermatologists for some severe, unusual disorders.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Thalidomide in the treatment of cancer.

Thalidomide caused severe malformations in babies born to mothers taking the drug for morning sickness in the late 1950s and early 1960s. It is now known that these teratogenic effects are due to potent anti-angiogenic and immunomodulatory actions. These properties have lead to the testing of thalidomide in a number of infective, inflammatory and malignant conditions. Promising activity has been reported in myeloma, AIDS-related Kaposi's sarcoma, renal cell carcinoma and glioblastoma multiforme. A review is presented of the history of thalidomide and its recent development with an emphasis on applications in malignant disease.

Angiogenesis Inhibitors↗
PubMed2003

Thalidomide analogs as emerging anti-cancer drugs.

Recently, it has been demonstrated that a number of novel thalidomide analogs possess anti-cancer properties due to their T cell co-stimulatory, anti-angiogenic and/or anti-inflammatory effects. Based on such effects, a class of thalidomide analogs known as Immunomodulatory Drugs (IMiDs) have recently entered into phase I clinical trials for the treatment of a number of cancers. The lead IMiD CC-5013 (referred to clinically as REVIMID) is now entering phase III clinical trials for multiple myeloma and metastatic melanoma, while CC-4047 (ACTIMID) is currently under investigation in phase I/II and II trials for multiple myeloma and prostate cancer, respectively. The other group of compounds, classified as Selective Cytokine Inhibitory Drugs (SelCIDs), do not co-stimulate T cells, but have anti-inflammatory and anti-angiogenic properties. Moreover, a subset of SelCIDs has been found to possess direct anti-tumor activity both in vitro and in vivo. This minireview highlights the various mechanisms of action associated with these compounds and their subsequent clinical development. The enhanced efficacy and lower side-effect profiles of the analogs in comparison to thalidomide make the use of these agents very attractive as novel anti-cancer agents.

Adjuvants, Immunologic↗
PubMed2006

Should we screen patients for inherited thrombophilia before starting thalidomide?

The authors present a case of refractory multiple myeloma in an elderly patient with heterozygosity for the G20210A mutation of factor II and for the C677T mutation of methylenetetrahydrofolate reductase. This patient developed acute, multiple cerebral infarctions 5 months into the treatment with thalidomide. The patient improved on oral anticoagulation. The authors presume that thalidomide increased the risk of cerebral infarction in this predisposed patient. The presence of increased risk for thrombosis should alert clinicians to screen patients presenting with systemic thrombosis for inherited thrombophilia. This risk increases with the presence of diseases and therapies that predispose for a hypercoagulable state. They suggest that patients required to be on thalidomide should be screened for inherited thrombophilia and should be considered for prophylactic anticoagulation therapy.

Administration, Oral↗
PubMed2006

Thalidomide-induced organizing pneumonia.

Twenty medications are associated with drug-induced organizing pneumonia; however, thalidomide is not listed as a potential causative agent. Thalidomide (Thalomid, Celgene Corp., Summit, NJ), an angiogenesis inhibitor and immunomodulator that reduces tumor necrosis factor-alpha, is used for the treatment of multiple myeloma. We report a case of organizing pneumonia in a 58-year-old male with multiple myeloma treated with dexamethasone and thalidomide.

Adult↗
PubMed2005

alpha-fetoprotein response predicts survival benefits of thalidomide in advanced hepatocellular carcinoma.

BACKGROUND: Radiographic measurements do not always reflect the biological response of hepatocellular carcinoma to drug therapy. AIMS: To evaluate the clinical implications of tumour marker (alpha-fetoprotein) response in advanced hepatocellular carcinoma patients with thalidomide treatment. PATIENTS AND METHODS: Forty-two advanced hepatocellular carcinoma patients with baseline alpha-fetoprotein levels above 200 ng/mL and thalidomide therapy were included. Serum alpha-fetoprotein levels were measured every 4 weeks. alpha-fetoprotein response was defined as a 50% or greater reduction of alpha-fetoprotein levels for 4 or more weeks during treatment. Radiographic response was assessed by World Health Organization criteria; survivals were estimated by Kaplan-Meier method and prognostic factors were assessed by Cox's proportional hazard model. RESULTS: With intention-to-treat analysis, radiographic response and alpha-fetoprotein response were obtained in 7% (three of 42, 95% confidence interval: 0-15) and 24% (10 of 42, 95% CI: 10-38) of patients, respectively. All radiographic response was observed in alpha-fetoprotein responders. Multivariate analyses showed alpha-fetoprotein response was independent prognostic factor for both progression-free survival (relative risk = 0.394, 95% CI: 0.189-0.820, P = 0.013) and overall survival (relative risk = 0.241, 95% CI: 0.096-0.606, P =0.003), whereas radiographic response was not. CONCLUSION: alpha-fetoprotein response can more accurately reflect the biological response of advanced hepatocellular carcinoma to thalidomide therapy than radiographic response.

Aged↗
PubMed2005

Thalidomide in the management of epidermolysis bullosa pruriginosa.

Epidermolysis bullosa (EB) pruriginosa is a distinctive clinical subtype of dystrophic EB. We report a patient with dominant dystrophic EB pruriginosa, who had an excellent response to systemic thalidomide treatment. The mechanism of action of thalidomide in the management of pruriginous disorders is not yet completely understood. Most recent studies point towards an immunomodulatory action of thalidomide that may suppress excessive production of tumour necrosis factor-alpha and may downregulate certain cell surface adhesion molecules involved in leucocyte migration.

Adolescent↗
PubMed2006

A child with laryngo-onychocutaneous syndrome partially responsive to treatment with thalidomide.

Laryngo-onychocutaneous syndrome (LOCS) is a condition characterized by erosive or ulcerative skin lesions associated with excessive granulation tissue, at sites of trauma such as the digits, elbows and knees. Similar lesions can occur within the conjunctival mucosa, leading to corneal scarring and blindness. The main complications, however, occur in the respiratory tract, where a similar process of erosions and subsequent formation of granulation tissue causes airway obstruction which may lead to premature death. LOCS is now believed to be a nonblistering variant of junctional epidermolysis bullosa and to date there are no efficacious treatments available. We report a 16-year-old girl with LOCS who failed to respond to methylprednisolone and cyclophosphamide, but had a partial response to oral thalidomide with marked decrease in granulation tissue and tracheal secretions. Interruption of treatment resulted in prompt resurgence of the granulation tissue which was again controlled by reintroduction of thalidomide. We propose that in the absence of effective therapies for LOCS, a trial of thalidomide in these patients should be considered.

Adolescent↗
PubMed2004

Early response predicts thalidomide efficiency in patients with advanced multiple myeloma.

Sixty-five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0.200/h, 0.140/h, 0.886 l/kg, 0.126 l/h/kg and 4.98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks.

Adult↗
PubMed2005

A non-randomised dose-escalating phase II study of thalidomide for the treatment of patients with low-risk myelodysplastic syndromes: the Thal-SMD-2000 trial of the Groupe Français des Myélodysplasies.

Patients (n=47) with low-risk myelodysplastic syndrome were treated with thalidomide [200 mg/d, increased by 200 mg/d/4 weeks up to week 16]. Responses were evaluated according to the International Working Group criteria at week 16 for 39 patients who received at least 8 weeks of treatment. Twenty-three (59%) patients showed haematological improvement (HI): four major erythroid response (HI-EM), 15 minor erythroid response, six major neutrophil response, two major platelet response. Side effects caused 22/39 to stop thalidomide before week 16. Nine of 23 responders continued thalidomide after week 16 [19% of trial patients] with sustained response in eight of nine. Six reached week 56, including the four HI-EM patients [13% of trial patients]. Nineteen of 36 red blood cell transfusion-dependent patients (53%) showed erythroid response, but only four became transfusion-independent. Among the 23 responders, the median duration of response was 260 d (range 30-650). Responses were sustained in all patients except one, and were observed between week 4 and week 8 in 85% of patients, at doses ranging from 200 to 400 mg. Only two patients responded at 600 mg/d and none at 800 mg/d. No clinical characteristics of responding versus non-responding patients were identified. The erythroid response rate was identical in all cytogenetic subgroups, including 5q31.1 deletions. Pretreatment vascular endothelial growth factor levels were lower in responders compared with non-responders (P=0.004). Microvessel density (MVD) increased and apoptosis decreased in four of six and in all six responders studied respectively whereas MVD and apoptosis were unchanged in three non-responders.

Aged↗
PubMed1976

Epilepsy: a neurological complication of thalidomide embryopathy.

The possibility of epilepsy resulting from maternal thalidomide ingestion was investigated by obtaining a telephoned neurological history from all suspect families in the United Kingdom in which the specific diagnosis was uncertain. The annual incidence in the first seven years of life was found to be five times the figure for the general population, and the prevalence of active epilepsy is significantly increased in the teenage thalidomide population. That this increased incidence and prevalence of epilepsy is not a chance observation is supported by published clinical and experimental evidence of central nervous system abnormalities in thalidomide embryopathy, in addition to the known neurological effects of the drug in the adult.

Adolescent↗
PubMed1994

Autism in thalidomide embryopathy: a population study.

Of a population of 100 Swedish thalidomide embryopathy cases, at least four met full criteria for DSM-III-R autistic disorder and ICD-10 childhood autism. Thalidomide embryopathy of the kind encountered in these cases affects fetal development early in pregnancy, probably on days 20 to 24 after conception. It is argued that the possible association of thalidomide embryopathy with autism may shed some light on the issue of which neural circuitries may be involved in autism pathogenesis.

Adult↗
PubMed1977

Linear growth of children with limb deformities following exposure to thalidomide in utero.

The growth of 202 children exposed to thalidomide in utero and having upper (139 children) or lower (63 children) limb deformities has been assess towards the end of pre-pubertal growth. The analyses show that children exposed to thalidomide are shorter than normal children but grow at a normal velocity later. These findings may help in consideration of the mechanism by which thalidomide exerted its teratogenic effect. Analyses of growth may find a wider use in the retrospective assessment of drugs which are potentially harmful in pregnancy.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Thalidomide in the management of recurrent aphthous ulcerations in patients who are HIV-positive: a review and case reports.

Recurrent Aphthous Ulceration (RAU) is an inflammatory ulcerative disease of unknown etiology. Although RAU are common in the general population, people with HIV disease may have ulcers that are large and painful and take a long time to heal. Local and systemic steroid therapy has been the traditional method of treatment for recurrent lesions. Recent studies have shown that systemic thalidomide therapy has the best efficacy in the treatment of major RAU in HIV-seropositive patients. Two case histories of complete resolution of the RAU are presented. We have included recommended guidelines for prescribing thalidomide according to the System for Thalidomide Education and Prescribing Safety (STEPS) Program.

Adult↗
PubMed1999

Lack of in vitro antimicrosporidian activity of thalidomide.

Thalidomide was evaluated for its in vitro activity against Encephalitozoon species by using the MRC-5 cell system. A cytotoxic effect was observed for concentrations of 10(1) microg/ml (P < 10(5)) and 5 microg/ml (P < 10(5)). Thalidomide did not significantly inhibit the growth of any of the microsporidia under study. These data suggest that thalidomide is not an etiologic treatment in microsporidial enteritis.

AIDS-Related Opportunistic Infections↗
PubMed2002

Use of IMiD3, a thalidomide analog, as an adjunct to therapy for experimental tuberculous meningitis.

Tuberculous meningitis (TBM), the most severe form of Mycobacterium tuberculosis infection in humans, is associated with significant morbidity and mortality despite successful treatment with antituberculous drugs. This is due to the irreversible brain damage subsequent to the local inflammatory response of the host to M. tuberculosis. Corticosteroids have been used in conjunction with antituberculous therapy in an attempt to modulate the inflammatory response, but this strategy has been of limited success. Therefore, we examined whether combining antituberculous drugs with the immunomodulatory drug thalidomide or with a new thalidomide analog, immunomodulatory drug 3 (IMiD3), would be effective in reducing morbidity and mortality in an experimental rabbit model of TBM. Intracisternal inoculation of 5 x 10(4) CFU of Mycobacterium bovis Ravenel in rabbits induced progressive subacute meningitis characterized by high cerebrospinal fluid (CSF) leukocytosis, protein influx, release of tumor necrosis factor (TNF), substantial meningeal inflammation, and mortality by day 28. Treatment with antituberculous drugs or with antituberculous drugs plus thalidomide improved the clinical course of disease somewhat and increased survival to about 50%. In contrast, treatment with antituberculous drugs in combination with IMiD3 limited pathological neurologic changes and resulted in marked improvement (73%) in survival. IMiD3 treatment was also associated with reduced leukocytosis in the CSF and significantly lower levels of TNF in CSF and plasma. Histologically, the meningeal inflammation in animals treated with antituberculous drugs plus IMiD3 was considerably attenuated compared to that of the other treatment groups. These results suggest a potential role for IMiD3 in the management of TBM in patients.

Animals↗