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Final Dose (final + dose)
Selected AbstractsA phase I clinical trial of the histone deacetylase inhibitor belinostat in patients with advanced hematological neoplasiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2008Peter Gimsing Abstract Purpose:, To determine the safety, dose-limiting toxicity and maximum tolerated dose (MTD) of the novel hydroxamate histone deacetylase inhibitor belinostat (PXD101) in patients with advanced hematological neoplasms. Patients and methods:, Sequential dose-escalating cohorts of three to six patients with hematological malignancies received belinostat administered as a 30-min i.v. infusion on days 1,5 of a 21-d cycle. Experience from a parallel dose-finding study in patients with solid tumors influenced the selection of the final dose. Results:, Sixteen patients received belinostat at one of three dose levels: 600 mg/m2/d (three patients), 900 mg/m2/d (three patients) and 1000 mg/m2/d (10 patients), the dose determined to be the MTD in a phase I solid tumor study [Steele et al. (2008) Clin Cancer Res, 14, 804,10]. The most common treatment-related adverse events (all grades) were nausea (50%), vomiting (31%), fatigue (31%) and flushing (31%). No grade 3 or 4 hematological toxicity compared with baseline occurred except one case of grade 3 lymphopenia. There were two related grade 4 adverse events of renal failure observed. Both events occurred in patients with multiple myeloma and had similar characteristics, i.e. an acute episode of decrease in renal function (pre-existing nephropathy in one patient), with a metabolic profile and decrease in tumor burden consistent with tumor lysis syndrome. No other related grade 4 events were noted. The only related grade 3 events noticed in more than one patient were fatigue and neurological symptoms (one patient had status epilepticus in association with uremia and one patient had paresthesia), all other related grade 3 events occurred in single patients. No cardiac events were noted. No complete or partial remissions were noted in these heavily pre-treated (median of four prior regimens) patients. However, five patients, including two patients with diffuse large-cell lymphoma [including one patient with transformed chronic myelomcytic leukaemia (CLL)], two patients with CLL and one patient with multiple myeloma, achieved disease stabilization in of two to nine treatment cycles. Conclusions:, Intravenous belinostat at 600, 900 and 1000 mg/m2/d is well tolerated by patients with hematological malignancies. The study was carried out in parallel to a similar dose-finding study in patients with solid tumors, in which the MTD was determined to be 1000 mg/m2/d days 1,5 in a 21-d cycle. This dose can also be recommended for phase II studies in patients with hematological neoplasms. [source] Methadone for refractory restless legs syndromeMOVEMENT DISORDERS, Issue 3 2005William G. Ondo MD Abstract Most cases of restless legs syndrome (RLS) initially respond well to dopaminergic agonists. However, an unknown percentage of patients is intolerant of dopaminergic adverse events, initially or subsequently refractory, or develops limiting augmentation. We administered methadone 5 to 40 mg/day (final dose, 15.6 ± 7.7) to 29 RLS patients who failed dopaminergics. They were currently taking or had previously tried 5.9 ± 1.7 (range, 3,9) different medications for RLS and 2.9 ± 0.8 (range, 2,4) different dopaminergics. Of the 27 patients who met inclusion criteria, 17 have remained on methadone for 23 ± 12 months (range, 4,44 months) at a dose of 15.5 ± 7.7 mg/day; 2 dialysis RLS patients died while on methadone, and 8 stopped the treatment (5 for adverse events, 2 for lack of efficacy, and 1 for logistical reasons). All patients who remain on methadone report at least a 75% reduction in symptoms, and none have developed augmentation. Methadone should be considered in RLS patients with an unsatisfactory dopaminergic response. © 2004 Movement Disorder Society [source] Safety and Efficacy of Intrathecal Baclofen Infusion by Implantable Pump for the Treatment of Severe Spinal Spasticity: A Spanish Multicenter StudyNEUROMODULATION, Issue 4 2000J Vidal MD Objective. To assess long-term efficacy, safety and functional benefit of intrathecal baclofen for severe spinal spasticity. Materials and Methods. This prospective multicenter study was performed in two stages: the first one consisted of an intrathecal bolus injection of baclofen, and the second of a continuous intrathecal baclofen infusion by means of an implantable pump. The sample consisted of 72 adult patients with severe spinal spasticity. Sixty-four were implanted and followed for 36 months. Muscular tone, spasms, and functional scales were evaluated before and periodically after administration of the drug, with a follow-up period of 36 months. Results. A very significant decrease in tone and spasms was observed in all cases (p < 0.001). Tolerance appeared during the first 12 months, increasing doses from a mean initial dose of 83.2 ,g (range 25,200 ,g) to a mean final dose of 270 ,g (range 25,800 ,g). Later on, efficacy remained stable, except in cases of mechanical problems of the infusion system. [source] HPA axis safety of fluticasone furoate nasal spray once daily in children with perennial allergic rhinitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2009Ita Tripathy The effects of intranasal corticosteroids (INSs) on the hypothalamic,pituitary,adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 ,g once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2,11 yr with a 1-yr history of PAR (6 months for patients aged 2,3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88,1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 ,g QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR. [source] Effect of crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in micePHYTOTHERAPY RESEARCH, Issue 5 2010Hossein Hosseinzadeh Abstract Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine-withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5,h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3,mg/kg) or normal saline. Naloxone was injected (5,mg/kg i.p.) 2,h after the final dose of morphine and the number of episodes of jumping during 30,mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30,mm prior and 1 and 2,h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320,mg/kg) and the ethanolic extract decreased it in the dose of 800,mg/kg in open field test. But crocin and the dose of 400,mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome. Copyright © 2009 John Wiley & Sons, Ltd. [source] Topiramate in the treatment of psoriasis: a pilot studyBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2002R. Ryback SummaryBackground This study was initiated following a serendipitous finding in which a patient who presented with both a mood disorder and psoriasis experienced significant improvement of her psoriasis following treatment with topiramate. Objectives To determine the efficacy of topiramate for the treatment of psoriasis. Methods Seven other patients, six of whom presented with both mood disorders and psoriasis and one with psoriasis only, were treated in an open-label fashion with topiramate. Topiramate therapy was usually initiated at 15 mg day,1 and gradually titrated by 15 mg week,1 to an average final dose of 56 mg day,1. Patients were treated for a minimum of 4 months. Psoriasis severity was measured using the psoriasis area and severity index (PASI). Results For all patients, the mean PASI score decreased from 16·1 before treatment to 7·1. For patients exhibiting improvement, the mean PASI score decreased from 14·3 to 3·9. Conclusions These results represent the first known report of the efficacy of topiramate in the treatment of psoriasis. [source] Levetiracetam monotherapy for childhood occipital epilepsy of gastautACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009A. Verrotti Objectives ,, The aim of this open label pilot study was to evaluate the efficacy and tolerability of levetiracetam (LEV) as ,de novo' monotherapy in children and adolescents with late onset childhood occipital epilepsy,Gastaut type (COE-G). Material and methods ,, Twelve patients suffering from COE-G were enrolled in this prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a peak of frequency at mean (±SD) 10.54 ± 2.77 years. Therapy with LEV was started at 10 mg/kg/day and, after titration, the final dose was generally achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day. Results ,, At the 6 month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month evaluation all patients were completely seizure free. Four patients (33.3%) continued to show some EEG abnormalities, while eight (72.8%) patients had normal EEG. At the 18-month evaluation all patients were seizure free and 10 patients (83.3%) showed a complete normalization of EEG abnormalities. Discussion ,, Monotherapy with LEV was effective and well tolerated in patients with COE-G. Nevertheless, prospective, large, long-term double-blind studies are needed to confirm these findings. [source] Conversion from valproic acid onto topiramate in adolescents and adults with epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009A. Schreiner Objective,,, To explore efficacy and tolerability outcomes of topiramate (TPM) in patients with epilepsy transitioning from valproic acid (VPA) because of insufficient efficacy and/or tolerability onto TPM. Methods,,, Multicenter, open label, single arm, non-interventional study examining patients (,12 years) with epilepsy, transitioning onto TPM from baseline mono-or combination therapy with VPA. TPM was added onto the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1,2 weeks, until a final dose between 50,200 mg/day was reached. Based on clinical judgment, the treating physician decided whether or not and when the existing AED treatment especially with VPA could be withdrawn. Documented were type and frequency of seizures, TPM dose, quality of life (QOLIE-10 questionnaire), subjective perception of improvement, and adverse events (AE). Results,,, One hundered and forty-seven patients (59% women, mean age 41 years) switched from baseline VPA treatment onto TPM because of insufficient efficacy (61%) and/or poor tolerability (81%). Average duration of follow-up was 20.3 weeks with an overall discontinuation rate of 16.3% of patients, mainly because of AE (in 8.2% of 147 patients). At study endpoint, the intended shift to TPM monotherapy was achieved in 70% of patients at a median dose of 150 mg/day. A seizure reduction of ,50% was achieved in 75% of patients in the last scheduled period (week 8,20), and 51% of patients entering that period remained seizure-free. Quality of life improved significantly as compared with baseline for all domains of QOLIE-10 (P < 0.001). Most frequent AEs were weight decrease (4.8%), paraesthesia and fatigue (4.1% each), speech disorder and headaches (2.7% each). Conclusions,,, In patients with epilepsy not satisfactorily treated with VPA, conversion to TPM was associated with improved seizure control as well as improvement in several aspects of quality of life. [source] | ||||||||||