Biomedical subjects

Ivo W Tremont-Lukats

Publications and source records attributed to Ivo W Tremont-Lukats.

8 recordsLinked to original sources

PubMed2006

A North American brain tumor consortium (NABTC 99-04) phase II trial of temozolomide plus thalidomide for recurrent glioblastoma multiforme.

BACKGROUND: Laboratory and clinical data suggest that the anti-angiogenic agent, thalidomide, if combined with cytotoxic agents, may be effective against recurrent glioblastoma multiforme (GBM). OBJECTIVES: To determine 6-month progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in adults with recurrent GBM. PATIENTS AND METHODS: Eligible patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was given at 150-200 mg/m(2)/day on days 1-5 of each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime (days 1-28) and increased to 1,200 mg as tolerated. Patients were evaluated with magnetic resonance imaging scans every 56 days. The study was designed to detect an increase of the historical 6PFS for GBM from 10 to 30%. RESULTS: Forty-four patients were enrolled, 43 were evaluable for efficacy and safety. The study population included 15 women, 29 men; median age was 53 years (range 32-84); median Karnofsky performance status was 80% (range 60-100%). Thirty-six (82%) patients were chemotherapy-naïve. There were 57 reports of toxicity of grade 3 or greater. Non-fatal grade 3-4 granulocytopenia occurred in 15 patients (34%). The objective response rate was 7%. The estimated probability of being progression-free at 6 months with this therapy is 24% [95% confidence interval (C.I.) 12-38%]. The median time to progression is 15 weeks (95% C.I. 10-20 weeks). There was no observed correlation between serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and the 6PFS outcome. CONCLUSION: This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.

Adult↗

PubMed2005

Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis.

We reviewed randomized controlled trials to determine the efficacy and safety of systemically administered local anesthetics compared with placebo or active drugs. Of 41 retrieved studies, 27 trials of diverse quality were included in the systematic review. Ten lidocaine and nine mexiletine trials had data suitable for meta-analysis (n = 706 patients total). Lidocaine (most commonly 5 mg/kg IV over 30-60 min) and mexiletine (median dose, 600 mg daily) were superior to placebo (weighted mean difference on a 0-100 mm pain intensity visual analog scale = -10.60; 95% confidence interval: -14.52 to -6.68; P < 0.00001) and equal to morphine, gabapentin, amitriptyline, and amantadine (weighted mean difference = -0.60; 95% confidence interval: -6.96 to 5.75) for neuropathic pain. The therapeutic benefit was more consistent for peripheral pain (trauma, diabetes) and central pain. The most common adverse effects of lidocaine and mexiletine were drowsiness, fatigue, nausea, and dizziness. The adverse event rate for systemically administered local anesthetics was more than for placebo but equivalent to morphine, amitriptyline, or gabapentin (odds ratio: 1.23; 95% confidence interval: 0.22 to 6.90). Lidocaine and mexiletine produced no major adverse events in controlled clinical trials, were superior to placebo to relieve neuropathic pain, and were as effective as other analgesics used for this condition.

Anesthetics, Local↗

PubMed2004

Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation.

The background to this study began with the reporting of two Japanese kindreds with the S305N tau mutation. Although the pathological findings in the autopsied cases were well characterized, only limited ante-mortem data were presented. In this study, longitudinal characterization was carried out in two siblings of European ancestry found to have frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) through comprehensive neurobehavioural examinations and other scales at approximate 6-month intervals. Scales included the Mini-Mental State Examination, Short Test of Mental Status, modified motor subtest of the Unified Parkinson's Disease Rating Scale, detailed neuropsychological testing, and the Neuropsychiatric Inventory. Changes in whole-brain volume and ventricular volume were measured from serial MRI studies. All members of the kindred underwent molecular genetic analyses to elucidate the mechanism of inheritance. The missense mutation in tau, S305N, was detected in the proband (onset age 30), who has undergone serial evaluations for almost 4 years. Her older sister (onset age 36) was subsequently found to have the same mutation, and has undergone serial evaluations for 2 years. This mutation is absent in both parents and the only other sibling, and non-paternity was excluded by additional analyses. The siblings have exhibited cognitive and behavioural features typical of FTDP-17, which have proved challenging to manage despite aggressive pharmacological and behavioural therapies. The proband's sister has demonstrated an atypical profile of impairment on neuropsychological testing. Both siblings have developed striking atrophy of the anterior part of temporal lobes and moderate atrophy of the dorsolateral and orbitofrontal cortical regions, which in both cases is relatively symmetrical. The annualized changes in whole-brain volume and ventricular volume, respectively, were -35.2 ml/year (3.23% decrease per year) and +20.75 ml/year (16.93% increase per year) for the proband, and -30.75 ml/year (2.77% decrease per year) and +5.01 ml/year (3.11% increase per year) for the proband's sister. In conclusion, the mutation in these siblings may have arisen during oogenesis in the mother and probably represents germline mosaicism. Although both patients have exhibited the typical cognitive and behavioural features of FTDP-17, one patient is exhibiting an atypical neuropsychological profile. Also, despite a similar topographic pattern of progressive atrophy on MRI, the rates of change in whole-brain volume and ventricular volume between the two patients are quite different. These findings have implications for future drug trial development in FTDP-17 and the sporadic tauopathies.

Adult↗

PubMed2003

Brain metastasis from prostate carcinoma: The M. D. Anderson Cancer Center experience.

BACKGROUND: The objective of this study was to estimate the incidence and describe distribution, clinical presentation, and prognosis of brain metastases in patients with prostate carcinoma who were seen at The University of Texas M. D. Anderson Cancer Center (MDACC). METHODS: The authors reviewed the charts of 16,280 patients with prostate carcinoma in the MDACC patient data base. Of 131 patients with craniospinal metastases confirmed by neuroimaging (n=53 patients) or autopsy (n=78 patients), 103 of 16,280 patients (0.63%) had parenchymal metastases. RESULTS: The median patient age at diagnosis was 64 years (range, 16-85 years). The median interval from the diagnosis of prostate carcinoma to the detection of brain metastasis was 35 months for patients with adenocarcinoma and 48 months for patients with small cell carcinoma (SCC). Confusion, headache, and memory deficits were the most frequent initial symptoms. Eighty-six percent of patients had single lesions, and 14% of patients had > or = 2 lesions. Metastases were supratentorial in 81 of 103 patients (76%), infratentorial in 22 of 103 patients (21%), and both supratentorial and infratentorial in 3 of 103 patients (3%). SCC and cribriform subtypes were more likely than adenocarcinoma to metastasize to the brain (relative risk, 20.36; 95% confidence interval, 9.91-41.84). Regardless of histology, the median survival in untreated patients was 1 month compared with 3.5 months in patients who were treated with radiotherapy. Patients who underwent stereotactic radiosurgery (n=5 patients) had a longer median survival (9 months). Survival was not affected by supratentorial or infratentorial location of metastases. CONCLUSIONS: Brain metastasis from prostate carcinoma is a rare, terminal event with death in <1 year frequently due to advanced, systemic disease. The majority of metastases were single and supratentorial. The most common clinical presentation was nonfocal neurologic symptoms related to intracranial hypertension. A better understanding of the biology of prostate carcinoma will help clarify the basis for its metastasis to the brain.

Adenocarcinoma↗

PubMed2003

Response of neoplastic meningitis from solid tumors to oral capecitabine.

Neoplastic meningitis (NM) is a major challenge for the neuro-oncologist as it constitutes a relatively common clinical problem in systemic and central nervous system cancers, and is very difficult to treat. NM portends a significant worsening in prognosis. Chemotherapeutic treatment options are limited, and not particularly effective. We report two cases of NM from breast carcinoma and a third with esophageal carcinoma, which responded to treatment with capecitabine, an oral prodrug for 5-flurouracil. We believe capecitabine warrants further investigation in patients with NM. In some patients, its use may result in clinical and radiographic tumor responses, improved quality of life, and possibly increased survival.

Administration, Oral↗

PubMed2002

Paraneoplastic chorea: case study with autopsy confirmation.

A 67-year-old man presented with a 7-month history of insidiously progressive chorea, ataxia, and vertigo. Neurologic examination revealed deficits referable to the basal nuclei, cerebellar vermis, and vestibular nuclei. Small-cell lung cancer was diagnosed by fine-needle biopsy of a parahilar mass. After chemotherapy, the patient's chorea worsened. Anti-Hu antibodies were present in serum and cerebrospinal fluid. Microscopic examination of the brain at autopsy revealed diffuse perivascular lymphocytic infiltrates, microglial activation, and neuronophagia throughout the neuraxis, including the brainstem, cerebellum, lenticular nuclei, striatum, and cerebral cortex. Prominent loss of Purkinje cells was seen in the cerebellar vermis and hemispheres to a lesser degree. Chorea is extremely rare as a paraneoplastic manifestation of cancer. The florid presentation and the positive findings contrasted with an unremarkable MRI of the brain. This case illustrates the preeminence of symptoms and signs over negative MRI findings in paraneoplastic encephalitis.

Brain↗

PubMedDate not supplied

A randomized, double-masked, placebo-controlled pilot trial of extended IV lidocaine infusion for relief of ongoing neuropathic pain.

OBJECTIVES: To determine the dose-response effect and safety of IV lidocaine at different dose infusion rates on spontaneous ongoing neuropathic pain. METHODS: In this double-masked, placebo-controlled, parallel study conducted in an outpatient clinical research center, patients with peripheral neuropathic pain received a 6-hour infusion of three doses (1, 3, and 5 mg/kg) of lidocaine or placebo. The main outcome measure was relief of pain intensity (percentage pain intensity difference [PID %]). Other measures were responder rate, adverse events, and correlation between lidocaine levels and PID %. RESULTS: There was a significant difference in the median PID % between the group treated with lidocaine 5 mg/kg/h (-34.60) and the placebo group (-11.96, P=0.012). Such effect began 4 hours after the onset of treatment and lasted until the end of the study. Lidocaine at lower infusion rates was no better than placebo in relieving pain. A modest but significant correlation was found between methylethylglycinexylidide (MEGX) levels and pain relief (R=0.60). There were no serious adverse events, but in two patients lidocaine was stopped prematurely. CONCLUSIONS: Lidocaine at 5 mg/kg/h was more effective than placebo at relieving neuropathic pain. The effect started 4 hours after the onset of treatment and continued for at least 4 hours after the end of the infusion. Additional research is needed using higher infusion rates with larger sample sizes to confirm these results and to explore the role of MEGX in the relief of neuropathic pain.

Adult↗

PubMedDate not supplied

Advances in molecular therapies in patients with brain tumors.

BACKGROUND: We are witnessing the development of new treatment modalities for primary brain tumors. An area under intense investigation is the use of small molecules targeting intracellular signaling pathways that interfere with growth, invasion, and metastasis of high-grade gliomas. METHODS: We review clinical trials of small molecules in adults with brain tumors. This search included electronic databases, specialty journals, textbooks, proceedings, and Web sites of the National Cancer Institute and other cooperative brain tumor groups in Europe and the United States. RESULTS: Several drugs with the ability to down-regulate the growth and invasion of malignant gliomas are at various stages of testing. Most of these focus on interfering with oncogenic and tumor survival pathways. Examples include inhibitors of tyrosine kinases, farnesyltransferases, and matrix metalloproteinases. These molecules are at different stages of testing, and a conclusive picture of which drug is most effective, either alone or in combination, needs better definition. The metalloproteinase inhibitor marimastat with temozolomide has given the best results to date in phase II trials, increasing the rate of 6-month progression-free survival for recurrent glioblastoma multiforme and anaplastic gliomas. CONCLUSIONS: As our understanding of the biology of gliomas increases and new drugs targeting specific molecular pathways enter well-designed cooperative trials, the control and prognosis of these tumors should improve.

Antineoplastic Agents↗