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Results for “Targeted dosing”

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At least 235 records · Page 13Linked to original sources

PubMed1996

Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study.

To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunction among consecutively screened patients with infarctions. A total of 2606 consecutive patients with left ventricular systolic dysfunction corresponding to an ejection fraction < or = 35% were identified. Of these patients, 1749 (67%) were randomly assigned to receive oral trandolapril or placebo beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular death (relative risk 0.75, p = 0.001), sudden death (relative risk 0.76, p = 0.03), and progression to severe/ resistant heart failure (relative risk 0.71, p = 0.003). Recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk 0.86, p = 0.29). More than 80% of patients in both treatment groups reached the target dose of 4 mg trandolapril or placebo at the end of dose titration. Nearly half of the patients in both treatment groups discontinued taking study medication before death or trial closure. The need for open-label ACE inhibition was the reason for discontinuation for 48 and 75 patients in the trandolapril and placebo groups, respectively. In conclusion, long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced mortality and morbidity. Most patients received the target dose of 4 mg trandolapril daily. The benefit observed is likely to reflect the benefit in clinical practice because the majority of eligible patients were randomized and the difference in patients leaving the trial to receive open-label ACE inhibition was moderate.

Aged↗

PubMed2002

Considerations on treatment efficiency of different conformal radiation therapy techniques for prostate cancer.

BACKGROUND AND PURPOSE: To evaluate the treatment efficiency of different conformal radiation therapy techniques in prostate cancer. MATERIALS AND METHODS: Three major classes of intensity-modulated radiation therapy (IMRT) delivery as well as a conformal rotation technique have been evaluated: sequential tomotherapy, dynamic multileaf collimation (DMLC) with conventional MLC, DMLC with miniMLC and dynamic field shaping arc. Treatment planning for the IMRT techniques has been performed with inverse planning. Forward planning was used for the dynamic arc technique. The four techniques have been compared to treat two different prostate cases with a conservative target dose of 70 Gy: a convex shaped target volume and one containing concavities formed by the bladder and rectum. Cumulative dose volume histograms, tumor control probability and normal tissue complication probability, conformity index and dose heterogeneity, and finally efficiency of treatment delivery have been evaluated. RESULTS: For the convex shaped target, all treatment modalities met the desired treatment goals, although the conventional MLC delivered more dose to the bladder. Compared to the dynamic arc modality, both tomotherapy and the conventional MLC technique needed a tenfold higher number of monitor units per target dose, and the miniMLC a twofold higher number. The same trend has been observed for the concave target, yet the dynamic arc did not meet the desired dose reduction for the rectum. The miniMLC configuration represented the best compromise for both targets with respect to treatment goals and delivery efficiency. Sequential tomotherapy performed adequately with respect to conformity at the cost of efficiency. CONCLUSIONS: Together with conformity and delivery efficiency the shape of the target should be considered as an important parameter in the selection of the treatment modality.

Humans↗

PubMed1987

Amphotericin-B nephrotoxicity in humans decreased by sodium supplements with coadministration of ticarcillin or intravenous saline.

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

Amphotericin B↗

PubMed1990

[Long-term results of postoperative and primary radiotherapy of carcinoma of the salivary glands: importance of dosage and target volume].

Longterm results in 92 patients after primary or postoperative irradiation for carcinoma of the major or minor salivary glands of the head are analyzed. Target volume included the region of the primary tumor; ipsilateral cervical lymph nodes were included in patients with metastases of the lymph nodes. Target doses were 25 to 35 X 2.0 Gy or in some cases 16 to 18 X 3.30 Gy. Local control was 93% in tumors of limited extension (I), 84% in extensive but macroscopically complete resected tumors (II) and 26% in biopsied or partially resected tumors (III). There were no major complications. Recurrence in the lymph nodes were observed in less than 5% of the group I + II NO and could be controlled permanently by secondary surgery plus irradiation. According to the own and published results the following target volumes are adequate: region of the primary tumor in adenoid-cystic carcinoma NO plus the ipsilateral cervical-supraclavicular region in patients with other high grade cancers or evidence for metastases. Target doses between 5940 and 7020 cGy are recommended.

Adenocarcinoma↗

PubMed2006

Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study.

OBJECTIVE: The main objective was to evaluate the safety and tolerability of prolonged-release nicotinic acid (niacin; Niaspan) in an usual care setting with patients receiving treatment for dyslipidaemia in Germany: the multiceNtre, open, uncontrolled sAfety and tolerability stUdy of a modified-release nicoTinic acId formuLation in sUbjects with dySlipidaemia and low HDL-cholesterol (NAUTILUS). RESEARCH DESIGN AND METHODS: This was a multicentre, open-label, 15-week study. Eligible patients had a diagnosis of dyslipidaemia with lipids inadequately controlled by 4 weeks of diet treatment. Additionally, patients had low HDL-cholesterol (< 1.03 mmol/L [< 40 mg/dL]) in men and < 1.29 mmol/L [< 50 mg/dL] in women), and had triglycerides < 9.03 mmol/L (< 800 mg/dL). Exclusion criteria included uncontrolled diabetes (HbA(1C) > 9%), significant hepatic, vascular or renal disease. The target dose was 2000 mg once daily. MAIN OUTCOME MEASURES: The main objective was to evaluate the safety and tolerability of prolonged-release nicotinic acid [incidence of adverse events (AE) and serious AE] in the overall population (the safety population). Efficacy parameters (lipid parameters) were also measured in the intent-to-treat population. RESULTS: A total of 566 patients were recruited, mostly with metabolic syndrome (39.4%), mixed hypercholesterolaemia (31.6%), isolated low HDL-cholesterol and markedly elevated cardiovascular risk for other reasons (10.8%), and primary hypercholesterolaemia (8.8%), according to NCEP/ATP III guidelines. The target dose was achieved by 65% of patients. Flushing was the most common side-effect (42%), as expected, and 9.7% withdrew for flushing. Other drug-related AEs occurred at low frequency (18.6%), and 8.7% withdrew for an AE other than flushing. Most AEs were mild or moderate in severity. Serious AEs considered possibly related to treatment occurred in three patients (0.5%); all resolved following treatment withdrawal. There was no hepatotoxicity or serious muscle AE. CONCLUSIONS: Prolonged-release nicotinic acid was well tolerated, and these results support its use in the management of patients at elevated cardiovascular risk due to low HDL-cholesterol.

Adult↗

PubMed1998

Toxicokinetics of organic solvents: a review of modifying factors.

This article reviews, with an emphasis on human experimental data, factors known or suspected to cause changes in the toxicokinetics of organic solvents. Such changes in the toxicokinetic pattern alters the relation between external exposure and target dose and thus may explain some of the observed individual variability in susceptibility to toxic effects. Factors shown to modify the uptake, distribution, biotransformation, or excretion of solvent include physical activity (work load), body composition, age, sex, genetic polymorphism of the biotransformation, ethnicity, diet, smoking, drug treatment, and coexposure to ethanol and other solvents. A better understanding of modifying factors is needed for several reasons. First, it may help in identifying important potential confounders and eliminating negligible ones. Second, the risk assessment process may be improved if different sources of variability between external exposures and target doses can be quantitatively assessed. Third, biological exposure monitoring may be also improved for the same reason.

Age Factors↗

PubMed2003

Negative correlation between therapeutic success in radioiodine therapy and TcTUs: are TcTUs-adapted dose concepts the only possible answer?

Calculation of iodine-131 activities for radioiodine treatment (RIT) in patients with disseminated thyroid autonomy may be difficult because of uncertainties in the determination of the autonomous volume (vol(aut)). The algorithm established by Emrich is used for calculation of the vol(aut) based on the TcTUs (technetium thyroid uptake under TSH suppression) (vol(aut)= 5xTcTUs+0.6). Clinical experience using this approach has shown that there is a negative correlation between increasing TcTUs and the results of RIT. Our aim was to identify the reasons for this observation as well as to assess the relation between TcTUs and sonographic vol(aut). Furthermore, we intended to find an alternative algorithm for the TcTUs-based calculation of the vol(aut). Data from 100 patients with unifocal autonomy who met strict inclusion criteria were used to evaluate the correlation between TcTUs and sonographic vol(aut). Using Marinelli's algorithm, we calculated the therapeutic activities for a standardised patient at a target dose of 300 Gy. The vol(aut) was determined based on the TcTUs using the four published algorithms [Emrich 1993 (vol(aut)= 5xTcTUs+0.6), Kreisig 1992 (vol(aut)=10xTcTUs-9.3), Joseph 1977 (vol(aut)=8.33xTcTUs-6.67) and 1994 (vol(aut)=2.88xTcTUs+0.09)]. We then compared the results of the calculation of therapeutic activities obtained using Emrich's algorithm (with known success rates) with those obtained by the other algorithms in order to determine which algorithm would lead to better results in RIT. Only a weak correlation was found between the TcTUs and the sonographic vol(aut) ( r(2)=0.39). The calculated therapeutic activities of (131)I were similar for all algorithms at a TcTUs of around 2% but Joseph's (1977) and Kreisig's (1992) algorithms resulted in clearly higher activities than Emrich's algorithm at a TcTUs above 2%. The need for target doses to increase with TcTUs in RIT may be overcome by the use of adequate algorithms for determination of the vol(aut). The algorithm published by Joseph and co-workers in 1977 probably offers the most reliable approach to the TcTUs-based calculation of vol(aut) in RIT. In contrast to the other algorithms, it is based on autoradiographic planimetric data. Thus, it takes into account the polyclonal origin of thyroid nodules as well as the presence of regressive or cystic changes. The well-established algorithm of Emrich underestimates the true vol(aut), which explains the decreasing success of RIT with increasing TcTUs.

Algorithms↗

PubMedDate not supplied

The AHCPR guidelines on heart failure: comparison of a family medicine and an internal medicine practice with the guidelines and an educational intervention to modify behavior.

OBJECTIVES: The objectives of this study were to apply the Agency for Health Care Policy and Research (AHCPR) guideline for heart failure to the measurement of quality of care in the ambulatory setting, to compare the results for two large practices and to design an educational intervention for the two practices being studied. METHODS: A retrospective chart review was conducted on a random sample of 50 patients with heart failure selected from each of two outpatient practices: the general internal medicine practice and the family medicine practice at a large academic medical center. Five medical review criteria were developed from the AHCPR guideline for heart failure to compare the two practices with each other and the guidelines. An educational intervention was developed to modify physician behavior in regard to compliance with guidelines. RESULTS: Assessment of left ventricular function occurred in 79% of all cases. Of eligible patients, 68% were treated with angiotensin-converting enzyme inhibitors (ACE-Is). Of those patients treated with enalapril and captopril, 30% and 12%, respectively, were receiving the target dose as defined in the AHCPR guidelines. Of patients not eligible for treatment with ACE-Is, none were treated with hydralazine and nitrates. When the ejection fraction was less than or equal to 40%, 81% of eligible patients were treated with ACE-Is, whereas 59% were treated with ACE-Is when the ejection fraction was greater than 40%. Calcium channel blockers were used in the treatment of 42% of patients. A statistical difference (P = .05) was found between the two practices for documentation of left ventricular function, the use of ACE-Is for patients with ejection fraction less than or equal to 40%, and the use of calcium channel blockers and beta blockers. CONCLUSIONS: In the practices studied, there is underutilization of the documentation of left ventricular function, ACE-Is in eligible patients, target doses of ACE-Is, and the use of hydralazine and nitrates for ineligible patients. A higher proportion of patients receive ACE-I therapy when the ejection fraction is less than or equal to 40%. There may be inappropriate use of calcium channel blockers in some patients. There is unexplained clinical variation between the two practices studied.

Adrenergic beta-Antagonists↗

PubMed2001

Assessment of the length of each hemodialysis session by on-line dialysate urea monitoring.

Hemodialysis (HD) prescription is usually based on the periodical measurement of the Kt/V achieved in a midweek dialysis session. The purpose of the study was to assess the duration of each HD session to achieve a target dose of dialysis. This allowed to determine whether a given dialysis session may be considered representative of the other HD sessions. Seventy-two HD sessions were studied in 4 stable patients, who were randomly dialyzed during 3 consecutive periods, each lasting 2 weeks, using a different blood flow rate (Qb) in each period: 400, 300 or 200 ml/min. All HD were prolonged to achieve an on-line dialysate urea monitor (UM) Kt/V of 1.2. The UM Kt/V was compared with the Kt/V calculated using pre-HD, post-HD and rebound (45 min post-HD) plasma water urea concentrations. Comparison of the duration of the second midweek dialysis session with the length of the other HD showed 95% concordance intervals (+/-2 SD) of +/-21.08 min for Qb 400, +/-26.88 min for Qb 300 and +/-37.02 min for Qb 200 ml/min. The 95% concordance intervals for whole body urea clearance were +/-32.0, +/-20.36 and +/-15.62 ml/min for Qb 400, 300 and 200 ml/min, respectively. No differences were observed between UM Kt/V and blood-based double-pool Kt/V obtained by the second-generation Daugirdas (1.18 +/- 0.08) and Garred (1.19 +/- 0.08) Kt/V formulas. In conclusion, a great variability was observed between different HD sessions with regard to the whole body urea clearance and the time required to attain a target Kt/V even when the HD characteristics remained constant. The length of every HD required to achieve a target dose of dialysis can be assessed by on-line dialysate urea monitoring.

Aged↗

PubMed2002

Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC.

UNLABELLED: The aim of this prospective phase II study was to evaluate the tumor response of neuroendocrine tumors to high-dose targeted irradiation with 7.4 GBq/m(2) of the radiolabeled somatostatin analog (90)Y-1,4,7,10-tetra-azacyclododecan-4,7,10-tricarboxy-methyl-1-yl-acetyl-D-Phe-Tyr(3)-octreotide (DOTATOC). In addition, we investigated the clinical benefit of (90)Y-DOTATOC regarding the malignant carcinoid syndrome and tumor-associated pain. METHODS: Thirty-nine patients (mean age, 55 y) with progressive neuroendocrine gastroenteropancreatic and bronchial tumors were included. The treatment consisted of 4 equal intravenous injections of a total of 7.4 GBq/m(2) (90)Y-DOTATOC, administered at intervals of 6 wk. After each treatment cycle, a standardized clinical benefit assessment using the National Cancer Institute grading criteria (NCI-CTC) was performed. RESULTS: The objective response rate according to World Health Organization (WHO) criteria was 23%. For endocrine pancreatic tumors (13 patients), the objective response rate was 38%. Complete remissions were found in 5% (2/39), partial remissions in 18% (7/39), stable disease in 69% (27/39), and progressive disease in 8% (3/39). A significant reduction of clinical symptoms could be found in 83% of patients with diarrhea, in 46% of patients with flush, in 63% of patients with wheezing, and in 75% of patients with pellagra. The overall clinical benefit was 63%. All responses (both clinical benefit and WHO response) were ongoing for the duration of follow-up (median, 6 mo; range, 2-12 mo). Side effects were grade 3 or 4 (NCI-CTC) lymphocytopenia in 23%, grade 3 anemia in 3%, and grade 2 renal insufficiency in 3%. CONCLUSION: High-dose targeted radiotherapy with 7.4 GBq/m(2) (90)Y-DOTATOC is a well-tolerated treatment for neuroendocrine tumors, with remarkable clinical benefit and objective response.

Carcinoid Tumor↗

PubMed2003

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

BACKGROUND AND PURPOSE: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). MATERIALS AND METHODS: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). RESULTS: A decrease of TC to <95% was found in 3/60 simulations (5%) of pulmonary and 7/58 simulations (12%) of hepatic targets. In two of 22 pulmonary targets (9%) and in four of 21 hepatic targets (19%) a TC of <95% occurred in at least one fraction. At risk for a decreased TC <95% were pulmonary targets with increased breathing mobility and hepatic targets with a CTV exceeding 100 cm(3). CONCLUSIONS: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV >or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.

Adolescent↗

PubMed1991

The objective evaluation of alternative treatment plans: II. Score functions.

A series of six patients with adenocarcinoma of the prostate, Stages A2, B1, or B2, were planned for treatment using a four-field box technique at 25 MV. Plans were prepared by three techniques: composite, mid-plane, and conformal. The dose distributions at the central plane and at two planes offset by +/- 2 cm were evaluated by means of score functions which quantify the magnitude of regret for target dose gradient, target over- and under-dose, non-target tissue overdose, and for overdose to the rectum, bladder, and femoral heads. The score functions are normalized to give values in the range from 10 (ideal) to zero (limit of acceptability), with negative values indicating unacceptable deviations from the prescribed dose limits. The scores for off-axis conformal plans were found to be essentially the same as for mid-plane plans on the central plane. However, mid-plane planning was shown to be totally inadequate for off-axis planes, where the average target gradient and underdose scores were reduced by 10 units. Composite planning resulted in adequate target coverage on all planes, but at the expense of unacceptable overdose to non-target tissue. The effect of reducing the posterior beam weight to half that of the other three beams was to reduce the target gradient score by 1.6 +/- 0.5 units and to increase the rectal score by 0.9 +/- 0.3 units.

Adenocarcinoma↗

PubMed2000

MERIT-HF--description of the trial.

The MERIT-HF study was a randomized, double-blind, placebo-controlled trial with a single-blind, two-week placebo run-in period. There were two primary objectives: total mortality; and the combined endpoint of total mortality or all-cause hospitalizations (time to first event). Several other combined endpoints were also predefined, as were number of hospitalizations due to heart failure and other cardiovascular causes, withdrawal of study medicine due to all causes, and due to worsening heart failure, and change in NYHA class. The effect on Quality of Life was assessed in a substudy. The major inclusion criteria were symptomatic heart failure for at least 3 months corresponding to NYHA class II-IV; and a left ventricular ejection fraction of 0.40 or less in 40 to 80 year old men and women. The patients had to be on optimal treatment for at least 2 weeks prior to randomization, defined in principle as any combination of diuretics and an ACE inhibitor. The recommended starting dose was half a 25 mg tablet of metoprolol CR/Zok once daily in patients in NYHA functional class III-IV, and one 25 mg tablet once daily in patients in NYHA class II. It was recommended to double the dose after each 2-week period in order to reach the highest tolerated dose aiming for a target dose level of 200 mg once daily of metoprolol CR/Zok or placebo. This dosage regimen could be modified according to the judgement of the investigator. Randomization began on February 14, 1997, and the last patient was randomized April 14, 1998. 1990 patients were randomized to metoprolol CR/Zok and 2001 to placebo. The International Steering Committee stopped the study by October 31, 1998, upon recommendation from the Independent Safety Committee. The second pre-planned interim analysis (50% point) had shown that the pre-defined criterion for termination of the study was met and exceeded. The mean follow-up time was 1 year.

Adrenergic beta-Antagonists↗

PubMed1992

The clinical application of a non-axial treatment plan for pancreatic and biliary malignancies.

Standard radiation therapy for adenocarcinoma of the pancreas treats a substantial portion of the renal parenchyma. It was hypothesized that rotating the plane of treatment to a non-axial orientation, with the anterior field entering the patient from an inferior oblique direction, would decrease the renal dose of radiation without increasing the liver dose or compromising the target dose. To test this hypothesis, patients referred for radical radiation treatment for tumors of the pancreas or distal common bile duct were prospectively evaluated by performing treatment planning using axial and non-axial field arrangements. Treatment plans were compared using dose volume histograms (DVHs) of both kidneys and the liver. In all 15 cases analyzed, the non-axial plan was superior to the axial plan with respect to renal dose, without significantly increasing the hepatic dose and was used for treatment. Treatment was not significantly more complex nor was gastrointestinal toxicity increased. These findings show that non-axial field arrangements can be used on a routine basis to decrease the renal dose of radiation for the treatment of pancreatic and biliary malignancies. It is anticipated that in the future, a combination of DVH-guided treatment planning and sophisticated renal function studies will be necessary to permit a more accurate prediction of the probability of renal complications resulting from radiation therapy.

Aged↗

PubMed1994

Organ-sparing treatment of advanced bladder cancer: a 10-year experience.

PURPOSE: Radical cystectomy is considered as standard therapy for muscle-invasive bladder cancer. We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy +/- chemotherapy. METHODS AND MATERIALS: From 1982 through 1991, 245 consecutive patients, mean age 66 years, with invasive bladder cancer (T2-3 or poor prognostic T1, no distant metastases) entered a prospective protocol with the objective of bladder preservation. Treatment consisted of transurethral resection (complete, if possible) and definitive radiotherapy with 56 Gy maximum dose (50.4 Gy minimum target dose) in 28 fractions. Since 1985, 139 patients received a simultaneous chemotherapy on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily (79 patients) or 65 mg/m2 carboplatin (60 patients). Cystectomy was performed as salvage treatment for residual or recurrent invasive disease. The median follow-up at the date of analysis (12-31-92) was 5.9 years. RESULTS: The overall survival was 47% after 5 years and 26% after 10 years. The 5-year survival according to the initial T-category was 60% for T1 (44 patients), 64% for T2 (47 patients), 43% for T3 (127 patients), and 16% for T4 (23 patients). The most important single prognostic factor was the amount of residual tumor after TUR (5-year survival 80% after R0, 53% after R1, and 31% after R2 resection, p < 0.01). Chemotherapy increased the rate of complete remission, but had no impact on 5-year survival (52% vs. 50%). Fifty-three salvage cystectomies were performed, all without severe complications, and 192 patients (79%) maintained a normal functioning bladder. The bladder preservation rate in 5-year survivors was 83%. CONCLUSIONS: Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective. The survival in this series is as good as in any comparable cystectomy series. Eighty-three percent of long-term survivors maintained their functioning bladders.

Aged↗

PubMed2004

Tolerability of carvedilol in heart failure: clinical trials experience.

An extensive clinical trials database now exists to support the therapeutic efficacy of beta-blockers in systolic heart failure. However, concerns remain about the tolerability of these agents. These concerns relate to perceived complexity in initiation and uptitration, risk of worsening heart failure clinical status, and delay in beneficial effects on outcomes. All of the above concerns are thought especially relevant in patients with advanced disease. However, these perceptions are not borne out in the controlled clinical trial experience or in open-label studies and postmarketing surveillance programs with carvedilol. Specifically, in clinical studies, discontinuation rates (because of adverse events), serious adverse event rates, mean achieved dose, and percentage reaching target dose strongly suggest good tolerability. This is especially notable, considering that beta-blockade is used in addition to other background neurohormonal antagonists, such as angiotensin-converting enzyme inhibitors. Furthermore, tolerability in the everyday community setting also appears to be high. Carvedilol, specifically, is also well tolerated during initiation of therapy, with fewer withdrawals for heart failure during the first 8 weeks of uptitration, and no delay in the accrual of beneficial clinical outcomes, as observed in the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. Thus, in contrast to widely held perceptions about tolerability of beta-blockade in heart failure, carvedilol appears to be an extremely well-tolerated agent, even during initiation and in the most advanced patients.

Adrenergic beta-Antagonists↗

PubMed2005

Reduced-intensity conditioning allogeneic blood stem cell transplantation with fludarabine and oral busulfan with or without pharmacokinetically targeted busulfan dosing in patients with myeloid leukemia ineligible for conventional conditioning.

We prospectively compared outcomes after a fludarabine (Flu) plus oral busulfan (Bu)-containing reduced-intensity conditioning regimen (150 mg/m2 Flu and 10 mg/kg oral Bu), with (n = 32; Flu- T Bu group) or without (n = 30; Flu-Bu group) therapeutic dose monitoring and dose adjustment of Bu. All patients received peripheral blood stem cells from a genoidentical sibling, and study cohorts had similar patient characteristics. Dose adjustments of Bu were required in 20 (63%) patients in the Flu- T Bu group (median final dose, 8.89 mg/kg; range, 6.3-13.34 mg/kg). Donor T-cell and granulocyte engraftments were similar, and early conditioning-related toxicities were mild and similar in both study groups. With a median follow-up of 45 months (51 months in the 37 survivors), posttransplantation outcomes did not differ between cohorts. The strongest predictor of 2-year overall survival and leukemia-free survival was the presence of chronic graft-versus-host disease (77% versus 34% for overall survival and 74% versus 34% for leukemia-free survival; P < .001 for both outcomes). In conclusion, therapeutic dose monitoring of oral Bu in a reduced-intensity conditioning setting does not seem to affect outcome, although further studies may identify very-high-risk patients who benefit from this strategy.

Administration, Oral↗

PubMed2006

[Image-guided radiotherapy by in-room CT-linear accelerator combination].

Target localization has become increasingly important in the advent of IMRT, as treatment margins are reduced and target doses are increased with high-dose gradients outside this target volume. The in-room CT on rails-LINAC system allows CT imaging while the patient remains immobilized in the treatment position just prior to treatment. The anatomic inter- and intra-fractional variations can be therefore quantified during a course of treatment. The position of the tumour can be checked and corrected before the fraction. In case of modification of tumour shape, a re-planning of the treatment is also feasible. However, several issues remain: the integration with routine clinical treatment due to a lack of software tools, the frequency of imaging, and the cost-efficiency ratio. The clinical experience is yet very limited but CT-image-guided radiotherapy appears promising for prostate, brain and spinal tumours.

Brain Neoplasms↗