Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THALIDOMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources
PubMed2001

Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma.

We have explored the mechanism of the antiangiogenic effects of thalidomide by structure-activity studies. These investigations revealed that angiogenesis inhibition correlates with teratogenicity but not with tumor necrosis factor-alpha (TFA-alpha) inhibition. Additionally, one analog of thalidomide, 3-aminothalidomide, exhibited an unusual capacity to directly inhibit myeloma cell proliferation. This activity did not correlate with TNF-alpha inhibition. Thus 3-aminothalidomide was found to inhibit multiple myeloma through effects on both the tumor and vascular compartment. The effects of an inhibitor of both the tumor and vascular compartments of a tumor on tumor growth may be synergistic.

Angiogenesis Inhibitors↗
PubMed1999

Inhibition of TNF-alpha synthesis with thalidomide for prevention of acute exacerbations and altering the natural history of multiple sclerosis.

Multiple sclerosis (MS) is a common neurological disorder which has a relapsing/remitting course and is presently incurable. A variety of agents have been tried to prevent excerbations and alter the natural history of the disease. Tumor necrosis factor-alpha (TNF-alpha) has been implicated as the most important cytokine in the pathogenesis of MS. There is evidence that thalidomide is an agent which blocks production of TNF-alpha by a mechanism different from other agents. Hence it is hypothesized that using thalidomide as therapy would prevent acute exacerbations of MS as well as alter its natural history.

Disease Progression↗
PubMed1984

[Gynecological and endocrinological studies of thalidomide-damaged girls].

Gynaecological examinations were done for the first time in 32 girls, between age 13 and age 18 damaged by thalidomide. 11 of the girls had primary amenorrhoea at the time of examination. 9 of these cases showed genital malformations. 7 cases showed aplasia of the uterus. A rudimentary uterus and a hypo-plastic uterus were found in one patient each. In 8 girls these changes were combined with abnormalities of the vagina, 3 cases had vaginal aplasia. 4 cases had a blind vaginal sac. 1 case had a urogenital sinus. Two patients had primary amenorrhoea without genital malformations. In the girls who had started menstrual periods none of the 21 cases showed genital malformations. Supplementary endocrinological investigations were done to answer the question whether functional disturbances were caused by thalidomide in addition to organic changes. The development of puberty can be diagnosed from secondary sexual markers. Our patients had almost all advanced puberty with more mammary development than pubic development. The menarche between age 11 and age 16 showed no deviation from the normal in our patients. 11 girls had regular cycles. The hormonal vaginal cytology in 28 patients showed no sign of deficient estrogen. Neuro-endocrine maturation is responsible for the development of puberty. The basal secretions of FSH and LH increase. The dynamic functional test with LHRH shows the LH reserve of the pituitary which rises in a typical pattern. 14 patients had a LHRH test and nine of these showed a mature LH reserve corresponding to the index R2.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed2003

Thalidomide for treatment of severe generalized discoid lupus lesions in two patients with systemic lupus erythematosus.

We describe 2 patients with systemic lupus erythematous whose widespread discoid lupus erythematosus was unresponsive to systemic steroids and antimalarial agents. They showed dramatic improvement to thalidomide at a dose of 300 mg/d, with maximum benefit achieved within 15 weeks of therapy. Dosages of 50 to 100 mg/d were effective in maintaining remission for 1 year. However, thalidomide-induced neuropathy was observed in both cases.

Adult↗
PubMedDate not supplied

The clinical course of a child with CINCA/NOMID syndrome improved during and after treatment with thalidomide.

Chronic, infantile, neurological, cutaneous, and articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID), is a rare autosomal dominant inherited disease. It is characterized by a persistent rash with onset during the neonatal period, neurological and ocular manifestations, and articular involvement with abnormal ossification. Mutations within the CIAS1 gene are found in up to 60% of CINCA cases, but the exact underlying pathogenetic mechanisms causing this disorder are still unclear. Although the interleukin-1 (IL-1) receptor antagonist anakinra (rHuIL-1Ra) has recently been reported to be effective, no formal recommended treatment protocols exist thus far. Herein, we describe a 17-year-old girl with CINCA for whom numerous medication trials had been unsuccessful. After the introduction of thalidomide, the symptoms of arthropathy improved dramatically even months after the medication was discontinued by the patient. We propose that thalidomide can be beneficial in select patients with CINCA syndrome.

Adolescent↗
PubMed2002

Production of proangiogenic cytokines during thalidomide treatment of multiple myeloma.

Recently a growing number of studies have suggested the efficacy of thalidomide (THAL) in the treatment of relapsed or resistant multiple myeloma. Some of these studies indicate that the thalidomide antimyeloma effect is associated with decreased vessel density. Here we first present our experience with THAL treatment and then focus on the determination of the role of proangiogenic cytokines during THAL therapy. Thirty relapsing or resistant multiple myeloma (MM) patients were treated with THAL at a median dose of 400 mg/daily. Eighteen responded to THAL therapy and 12 were resistant or intolerant to THAL. We determined the plasma level of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) as the main biological parameters associated with tumour angiogenesis. In addition I1-6 and TNFalpha levels were also assayed. Assessment of peripheral blood (PB) and bone marrow (BM) cytokine levels were done before and during THAL treatment at weeks 4 and 8 of therapy. In the responder group VEGF, bFGF I1-6 and TNFalpha concentrations were significantly decreased after four weeks of therapy both in PB and BM. In the non-responder group no significant changes in bFGF and VEGF levels were observed. However, a significant increase in IL-6 and TNF concentrations was evident. We conclude that the significant decrease of VEGF, bFGF, I1-6 and TNFalpha concentrations reflected response to THAL therapy. Also it seems that VEGF is a better marker of response to treatment than bFGF.

Adult↗
PubMed2004

Thalidomide is highly effective in a patient with meningeal acute myeloid leukaemia.

We report a case of secondary acute myeloid leukaemia (AML) following high dose therapy for diffuse large B-cell non-Hodgkin's lymphoma (NHL) who developed meningeal leukaemia. This was refractory to systemic and intrathecal chemotherapy and cranial irradiation. Thalidomide has been reported to have anti-AML activity and appears to cross the blood brain barrier (BBB). We, therefore, attempted a trial of oral Thalidomide and achieved rapid biochemical and cytological remission with a short course. The patient, however, progressed systemically and succumbed to her illness.

Adult↗
PubMed2005

Very good partial response in a patient with MALT-lymphoma of the lung after treatment with low-dose thalidomide.

Pulmonary MALT lymphoma is a rare disease entity and generally follows an indolent clinical course. Due to scarce information from randomized prospective trials, no standardized therapy protocols exist. Besides irradiation and chemotherapy, novel biological agents such as the anti CD20-antibody rituximab and thalidomide constitute a promising new approach. In this report we demonstrate the case of a 52-year-old male patient with extra-intestinal MALT lymphoma of the lung. After 10 months of treatment with low dose thalidomide (100mg/d), very good partial response of the intrapulmonary lesions was achieved.

Humans↗
PubMed1998

A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death.

Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.

Animals↗
PubMed2005

Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects.

BACKGROUND: We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated. PATIENTS AND METHODS: Patients with advanced breast cancer were randomized to receive oral C (50 mg daily) and M (2.5 mg twice daily on days 1 and 4) (arm A) or the same regimen plus thalidomide (200 mg daily) (arm B). RESULTS: The mean VEGF level decreased from 378.9 (+/-274.4) pg/ml at baseline to 305.9 (+/-203.6) pg/ml at 2 months (P<0.001), with similar change with respect to baseline in both arms. In 171 evaluable patients we observed three complete remissions (CR) in both arms A and B, 15 partial remission (PR) in arm A and seven in arm B, for an overall response of 20.9% [95% confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8% to 20.6%) in arm B. The clinical benefit (CR+PR+SD>or=24 weeks) was 41.5% for both arms. Toxicity was generally mild. Higher neurological toxicity (2% versus 60%; P<0.0001) and constipation (8% versus 51%; P<0.0001) was observed in arm B. CONCLUSIONS: Metronomic low-dose CM induced a drop in VEGF, and was effective and minimally toxic. The addition of thalidomide did not improve results.

Administration, Oral↗
PubMed2000

New therapies for heart failure: is thalidomide the answer?

The syndrome of advanced heart failure is associated with considerable morbidity and mortality. Ideas about the reasons for the progressive nature of the heart failure syndrome have changed over the years, with the initial view that progression was principally due to pump failure (the 'haemodynamic' hypothesis), giving way to more modern views, which implicate neuro-endocrine activation (including catecholamine excess, renin-angiotensin system activation, etc.). More recently, an excess of inflammatory cytokines has been found in advanced heart failure and implicated in the progression of the disease. Amongst the cytokines found, TNF-alpha seems to be particularly important. The principle therapeutic action of thalidomide appears to be reduction of TNF-alpha levels. We therefore suggest that there may be a role for thalidomide, or its derivatives, in the management of advanced heart failure.

Heart Failure↗
PubMed2004

Combined effect of recombinant CD19 x CD16 diabody and thalidomide in a preclinical model of human B cell lymphoma.

Combining different treatment strategies offers the possibility of improving treatment results for cancer patients. The aim of our study was therefore to investigate the combination of treatment of established s.c. human B non-Hodgkin's lymphoma in severe immune deficient mice using a recombinant bispecific CD19 x CD16 diabody (targeting natural killer cells to CD19 cells) and the angiogenesis inhibitor thalidomide. Monotherapy with either thalidomide or diabody caused an approximate 50% reduction in tumor growth rate. The combined treatment showed evidence for a synergistic effect resulting in a 74% reduction in median tumor size. In the combined treatment group, two of five animals had complete remissions of their s.c. tumor. These results suggest that a combination treatment with recombinant diabodies and angiogenesis inhibition represents a useful approach in cancer therapy.

Animals↗
PubMed2006

Treatment of chronic transfusion-dependent gastric antral vascular ectasia (watermelon stomach) with thalidomide.

Gastric antral vascular ectasia (GAVE) is a rare condition causing chronic GI blood loss that often proves difficult to treat. Many patients require repeated transfusions despite best efforts made with endoscopic and pharmacological therapies. We attempted to manage a patient with endoscopic resistant GAVE with Thalidomide. Within 3 months the patient became transfusion independent and has maintained an adequate haemoglobin for 9 months on the Thalidomide therapy.

Anemia, Refractory↗
PubMedDate not supplied

Treatment of pediatric ocular melanoma with high-dose interleukin-2 and thalidomide.

Uveal melanoma is the most common primary ocular malignancy, although it is rare in children, and patients presenting with metastatic disease have a median survival of only 2 to 5 months. The tumor is generally unresponsive to systemic chemotherapy, but immunotherapy may be effective in selected patients. This report describes an 8-year-old girl with metastatic uveal melanoma treated with high-dose, bolus interleukin-2 (IL-2) and the antiangiogenic agent thalidomide. She tolerated treatment well and initially responded with stable disease in the liver and pancreas for 23 months. New pulmonary metastases developed and she was re-treated with high-dose IL-2, resulting in regression of her liver lesions and stable pulmonary disease for more than 18 months. These results suggest that IL-2 at high doses, and in combination with thalidomide, may be useful for uveal melanoma with tolerable side effects in children. Further study of this combination in children with immune-responsive tumors is warranted.

Angiogenesis Inhibitors↗
PubMed2006

First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma.

BACKGROUND: Bone involvement is frequently observed in multiple myeloma (MM) patients both at diagnosis and during the course of the disease. The evaluation of biochemical markers of bone turnover could allow a dynamic evaluation of the effects of a given therapy on bone metabolism. METHODS: In the present study, markers of bone resorption [urinary free pyridinoline (PYD), deoxypyridinoline (DPYD), N-terminal telopeptide of collagen I (NTX) and C-terminal telopeptide (serum crosslaps)] and of bone formation [bone alkaline phosphatase (BAP) and osteocalcin] were evaluated at diagnosis and after induction therapy in 40 patients (23M, 17F, median age = 53.5 yr) enrolled in the 'Bologna 2002' clinical trial. By study design, all patients received 4 months of combined thalidomide (100 mg/d for 2 wk then 200 mg/d), dexamethasone (40 mg/d on days 1-4, 9-12, 17-20/28 on odd cycles and on days 1-4 on even cycles) and zoledronic acid (4 mg/28 d). RESULTS: At diagnosis, although bone resorption markers were increased in more than 40% of the patients, only NTX (P = 0.029) and crosslaps (P = 0.000) were significantly related to the extent of skeletal lesions, as assessed by X-ray. After 4 months of therapy, a significant decrease in mean (+/-SE) urinary NTX (52.7 +/-6.9 nmol/mmol creatinine +/-6.9 vs. 14 +/- 1.42 nmol/mmol creatinine, P = 0.000) and serum crosslaps (6242.4 +/-945 pmol/L vs. 1414.9 +/- 173.8 pmol/L, P = 0.000) was observed in patients obtaining > or =partial response, at variance to what has been detected in patients showing <partial response. CONCLUSIONS: Among all bone resorption markers, urinary NTX and serum crosslaps seem to be strictly related to the extent of bone involvement in MM. Combined thalidomide + dexamethasone and zoledronic acid seem to be highly effective in reducing bone resorption in sensitive patients, although the relative contribution of each drug cannot yet be determined.

Adult↗
PubMed1983

Thalidomide in actinic prurigo.

Fourteen patients suffering from actinic prurigo were treated with thalidomide. Eleven patients showed lasting improvement on the drug and three of these remained symptom-free after discontinuing therapy. No major side-effects were observed. Thalidomide is an effective drug in the treatment of actinic prurigo but it must be used with adequate contraception in women of child-bearing age.

Adolescent↗