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PubMed1988

Hydroxydesipramine in the elderly.

Elevation of the hydroxy metabolites of the tricyclic antidepressants in the elderly has been demonstrated for nortriptyline and suggested for desipramine by a study reporting elevated hydroxydesipramine (OH-DMI) plasma levels in four older patients. In the current study, patients treated with desipramine (DMI) were studied to determine whether OH-DMI was elevated in two larger samples of depressed elderly patients and to determine the magnitude of the increase, if present. In Sample I, which consisted of 68 patients of whom 23 were over 60 years of age, a fixed target dose of DMI was employed. Sample II, in which 20 of the 56 patients were over 60, received a dose adjusted to attain a fixed target DMI blood level. OH-DMI levels were higher in patients over 60 than in younger patients but the differences were not significant in either sample individually. In the two samples combined, average OH-DMI levels were 11 ng/ml higher in patients over 60 and the difference was significant (t = 2.30, p = 0.02). If variations in dose are accounted for, OH-DMI concentrations are positively correlated with age in both samples. OH-DMI/DMI ratios were not higher in the patients over 60 in these samples, but OH-DMI/DMI ratios may be higher in patients on lower doses with low DMI levels, as is common in the treatment of elderly patients. If comparable dosage is administered, nonlinear increases in DMI levels result in lower OH-DMI/DMI ratios similar to those in younger patients. Although our findings of elevated hydroxy levels in the elderly are consistent with prior reports, the clinical importance of an 11 ng/ml difference, particularly in relation to total drug levels averaging 220 ng/ml, is questioned.

Administration, Oral↗

PubMed2003

Mirtazapine in essential tremor: a double-blind, placebo-controlled pilot study.

We sought to determine whether mirtazapine is safe and well-tolerated as a treatment for essential tremor (ET). We studied mirtazapine in a randomized, double-blind, placebo-controlled, crossover study of 17 ET patients. Patients were started with 15 mg per day of either mirtazapine or placebo for 1 week and the dose was escalated weekly until the targeted dose of 45 mg per day was achieved. This dose was maintained for 2 weeks. Tremor was assessed at baseline and after 14 days of 45 mg of mirtazapine or placebo. There was a minimum washout period of 14 days between the two arms of the study. Tremor assessments included global improvement, Fahn Tolosa Marin Tremor Rating Scale, Beck Depression Inventory and the Parkinson's Disease Questionnaire-39. Patient global improvement ratings indicated that in the placebo condition 12 patients were unchanged and 1 patient was mildly improved. In the mirtazapine condition, 10 patients were unchanged, 2 were moderately improved and 1 was markedly improved. There was no significant improvement with mirtazapine or placebo compared to baseline as measured by the Tremor Rating Scale. Adverse effects were more common in the mirtazapine group and included drowsiness, confusion, dry mouth, weight gain, polyuria, itching, nausea, gait and balance problems, blurred vision, and bad taste. We conclude that the majority of the ET patients do not benefit from mirtazapine. Mirtazapine has significant adverse effects and should be used cautiously in ET patients.

Aged↗

PubMed1996

Carboplatin pharmacokinetics in young children with brain tumors.

PURPOSE: The pharmacokinetic parameters and maximal tolerated systemic exposure were determined for carboplatin in young children given in combination with cyclophosphamide and etoposide. PATIENTS AND METHODS: Carboplatin was administered as part of a multiagent chemotherapy regimen to 21 pediatric patients less than 5 years of age with newly diagnosed, malignant central nervous system tumors. Patients, received cyclophosphamide, 1.2 g/m2, on day 1 and carboplatin on day 2 followed by etoposide, 100 mg/m2, each day. Carboplatin doses were calculated to achieve a targeted area under the serum concentration versus time curve (TAUC) of 5, 6.5 or 8 mg/ml.min based on each patient's measured glomerular filtration rate (GFR). Carboplatin pharmacokinetic parameters were determined after course 1 and then after every third course of therapy. RESULTS: The median carboplatin clearance and GFR after course 1 were 118 and 98 ml/min per m2, respectively. Targeted doses based on measured GFR reliably achieved the TAUC for carboplatin. The median (range) carboplatin clearance for four children less than 1 year of age was 76 (66-84) ml/min per m2, significantly lower (P = 0.05) than the value of 131 (80-158) ml/min per m2 for children from 1 to 4 years of age. The mean carboplatin clearance declined by 23% in 12 patients studied from course 1 to course 4 of therapy. The decrease was greater than 20% (range 20-53%) in 7 of the 12 patients studied. CONCLUSION: Carboplatin clearance for children aged between 1 and 4 years at diagnosis is approximately 45% higher than previously reported for pediatric patients, but declines after four courses of therapy. For children less than 1 year of age, carboplatin clearance per square meter is approximately 40% lower than patients 1 to 4 years of age. There are corresponding differences in GFR that provide a plausible explanation for the age and therapy-related changes in carboplatin clearance. Toxicity was acceptable for patients treated at a TAUC of 6.5 mg/ml.min for carboplatin given with etoposide and cyclophosphamide. The average carboplatin dose required for this AUC was 767 mg/m2.

Adolescent↗

PubMed1995

The implications for risk assessment of measuring the relative contribution to exposure from occupation, environment and lifestyle: hemoglobin adducts from amino- and nitro-arenes.

Recent progress in biomonitoring allows measurement of internal exposure of individuals ranging from occupational and life style exposures to environmental levels. Ten specific hemoglobin adducts generated by polycyclic and monocyclic nitro-arenes were measured in coke oven workers and residents living on ground contaminated with explosive wastes, respectively. Consistently, adducts were found in most 'exposed' as well as control individuals, interindividual variation being great. Adduct levels in the majority of exposed individuals were within the range of reference values (95 percentile). Although hemoglobin adduct levels do not directly reflect genotoxic potential and potency of the parent compounds, they correlate with the biologically active dose. On the basis of such target doses, the contribution of specific exposures relative to 'background' and to related chemicals can be assessed. The impact of 'relative risk' on risk perception and risk management is to provide a rationale for the application of the ALARA principle (As Low As Reasonably Achievable).

Carcinogens, Environmental↗

PubMed2001

Dosimetric verification of a dedicated 3D treatment planning system for episcleral plaque therapy.

PURPOSE: Episcleral plaque therapy (EPT) is applied in the management of some malignant ocular tumors. A customized configuration of typically 4 to 20 radioactive seeds is fixed in a gold plaque, and the plaque is sutured to the scleral surface corresponding to the basis of the intraocular tumor, allowing for a localized radiation dose delivery to the tumor. Minimum target doses as high as 100 Gy are directed at malignant tumor sites close to critical normal tissues (e.g., optic disc and macula). Precise dosimetry is therefore fundamental for judging both the risk for normal tissue toxicity and tumor dose prescription. This paper describes the dosimetric verification of a commercially available dedicated treatment planning system (TPS) for EPT when realistic multiple-seed configurations are applied. MATERIALS AND METHODS: The TPS Bebig Plaque Simulator is used to plan EPT at our institution. Relative dose distributions in a water phantom, including central axis depth dose and off-axis dose profiles for three different plaques, the University of Southern California (USC) #9 and the Collaborative Ocular Melanoma Study (COMS) 12-mm and 20-mm plaques, were measured with a diode detector. Each plaque was arranged with realistic multiple 125I seed configurations. The measured dose distributions were compared to the corresponding dose profiles calculated with the TPS. All measurements were corrected for the angular sensitivity variation of the diode. RESULTS: Single-seed dose distributions measured with our dosimetry setup agreed with previously published data within 3%. For the three multiple-seed plaque configurations, the measured and calculated dose distributions were in good agreement. For the central axis depth doses, the agreement was within 4%, whereas deviations up to 11% were observed in single points far off-axis. CONCLUSIONS: The Bebig Plaque Simulator is a reliable TPS for calculating relative dose distributions around realistic multiple 125I seed configurations in EPT.

Brachytherapy↗

PubMed1998

Use of biomarkers--new frontiers in occupational toxicology and epidemiology.

The incorporation of biomarkers into occupational toxicology and epidemiology some 25 years ago marked a turning-point for the discipline. The advances in molecular biology have provided new tools. At first, the major interest was in biomarkers of exposure, borrowing concepts from pharmacology, then it moved from the external estimates of exposure to internal measures of dose, and ultimately, to markers of target dose. Concerted efforts to measure carcinogens at the molecular level, e.g. DNA adducts, occupied a substantial fraction of the biomarkers work. In parallel, more quantitative and more sensitive end-points for etiological studies were sought earlier. Again, with advancing techniques in cytogenetics, extensive studies were conducted on such markers as sister chromatid exchanges (SCEs), micronuclei and other changes deemed to represent genomic damage. However, these types of end-points were quite unspecific for application to new hazards of uncertain human carcinogenic potential. Recent work focusing on more specific early-effect markers such as certain oncogenes and tumour-suppressor genes have substantial promise as shown by work with aflatoxins and vinyl chloride. Such studies have also enhanced mechanistic insight. The advances in molecular genetics have led to an upsurge in interest in most susceptibility factors, and identification of polymorphisms of various enzymes has become possible. Ongoing search for 'ultra-high risk' individuals may be fruitful, but probably only relevant to a small segment of potentially exposed populations. Factors associated with a small differential risk, however theoretically or mechanistically important, offer only little practical use.

Biomarkers↗

PubMed2003

Topiramate in the preventive treatment of episodic migraine: a combined analysis from pilot, double-blind, placebo-controlled trials.

The safety and efficacy of medications for preventive treatment of migraine is the subject of current concern and investigation in health care. Two single-center, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy patients with a diagnosis of migraine were randomly assigned to topiramate-treated and placebo groups. The studies consisted of a 4-week baseline phase, a 6-8 week titration, and 8-12 weeks of maintenance. Topiramate was titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The primary efficacy measure, the mean 28-day migraine frequency, was lower in topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001). Similarly, topiramate treatment resulted in a significantly greater mean reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was the most common side effect reported with topiramate treatment. Other topiramate-associated adverse events included altered taste, memory impairment, diarrhea, and appetite suppression/weight loss. The rates of discontinuation were similar for the topiramate group (n=10) and the placebo group (n=8). These results suggest that topiramate is effective and well tolerated in the preventive treatment of migraine headaches.

Adult↗

PubMed2006

Maintenance thalidomide following single cycle autologous peripheral blood stem cell transplant in patients with multiple myeloma.

Although autologous stem cell transplant is an effective therapy for patients with multiple myeloma and extends progression-free survival (PFS) and overall survival (OS), patients show a continued pattern of recurrent disease. Twenty-nine patients were enrolled in a phase II study investigating the tolerability and efficacy of maintenance thalidomide following single autologous peripheral blood stem cell transplant. Six to eight weeks after transplant, patients were started on maintenance thalidomide at 50 mg a day. The dose was gradually escalated to a target dose of 400 mg a day and continued until disease progression or 6 months after achieving complete remission (CR) for a maximum total duration of 18 months. At 6 months, 13 patients (45%) achieved CR or near complete remission (positive immunofixation without any evidence of disease). The estimated 2-year OS was 83% and PFS was 49%. Median tolerated dose of thalidomide was 200 mg a day. In conclusion, thalidomide as maintenance therapy is feasible and may improve outcome after single autologous stem cell transplant.

Aged↗

PubMed2001

Use of biomarkers in risk assessment.

The systematic development and application of biomarkers in environmental health risk assessment is a relatively new field. At first, the major interest was in biomarkers of exposure, borrowing concepts from pharmacology, then it moved from the external estimates of exposure to internal measures of dose, and ultimately, to markers of target dose. While these markers provide evidence of exposures, they do not provide evidence of that toxicological damage has occurred. For this reason, measurements of DNA adducts and protein adducts are of interest, since they may provide bridges between exposures and disease end-points. In parallel, more quantitative and more sensitive end-points for diseases have been sought. Again, with advancing techniques in cytogenetics, extensive studies were conducted on such markers as chromosomal aberrations, micronuclei and other changes deemed to represent genomic damage. However, these types of end-points are quite unspecific for application to new hazards of uncertain human toxic (carcinogenic) potential. Recent work focusing on more specific early-effect markers such as certain oncogenes and tumour-suppressor genes have substantial promise as shown by work with aflatoxins and vinyl chloride. Such studies have also enhanced mechanistic insight. The advances in molecular genetics have led to an upsurge in interest in most susceptibility factors, and identification of polymorphisms of various enzymes has become possible. Ongoing search for "ultra-high risk" individuals may be fruitful, but probably only relevant to a small segment of potentially exposed populations. Factors associated with a small differential risk, however theoretically or mechanistically important, offer only little practical use.

Aflatoxins↗

PubMed2003

Random and systematic beam modulator errors in dynamic intensity modulated radiotherapy.

This paper reports on the dosimetric effects of random and systematic modulator errors in delivery of dynamic intensity modulated beams. A sliding-widow type delivery that utilizes a combination of multileaf collimators (MLCs) and backup diaphragms was examined. Gaussian functions with standard deviations ranging from 0.5 to 1.5 mm were used to simulate random positioning errors. A clinical example involving a clival meningioma was chosen with optic chiasm and brain stem as limiting critical structures in the vicinity of the tumour. Dose calculations for different modulator fluctuations were performed, and a quantitative analysis was carried out based on cumulative and differential dose volume histograms for the gross target volume and surrounding critical structures. The study indicated that random modulator errors have a strong tendency to reduce minimum target dose and homogeneity. Furthermore, it was shown that random perturbation of both MLCs and backup diaphragms in the order of sigma = 1 mm can lead to 5% errors in prescribed dose. In comparison, when MLCs or backup diaphragms alone was perturbed, the system was more robust and modulator errors of at least sigma = 1.5 mm were required to cause dose discrepancies greater than 5%. For systematic perturbation, even errors in the order of +/- 0.5 mm were shown to result in significant dosimetric deviations.

Brain Neoplasms↗

PubMed1995

Neurohormonal modulation in heart failure: ACE inhibition and beyond.

Angiotensin converting enzyme (ACE) inhibition undoubtedly has become the cornerstone of heart failure treatment. Useful in each stage, it should possibly be considered first-line treatment in many patients with mild heart failure in whom fluid retention is not clearly present. Careful consideration of the optimal dose for the individual is important. Until further data are available concerning the efficacy and tolerability of high and low doses, the clinician should consider the target doses used in large controlled heart failure trials. Even under optimal dosing conditions, it is likely that ACE inhibition may not suffice in completely modulating the extensive neurohormonal stimulation extant in heart failure. In part this may result from a breakthrough of the ACE inhibitor effect as well as from activation of hormones and peptides that may not be affected by ACE inhibition. Also, a substantial proportion of patients may not tolerate sufficient ACE inhibition. Alternative or additional therapy aimed at modulating neurohormonal activation concerns interference with other parts of the renin angiotensin system, such as angiotensin II receptor and aldosterone receptor antagonism. Sympathetic activity and catecholamine levels may decrease with dopaminergic D2 agonists and, possibly, beta-blockade; in the latter, this may be confined to patients with pre-existing sympathetic over-activation. Increasing circulating levels of atrial natriuretic peptide via neutral endopeptidase inhibition may offer an alternative way to increase diuresis and natriuresis without neuroendocrine stimulation. Novel possibilities that have not yet been tested sufficiently in patients with heart failure include endothelin receptor antagonism, arginine vasopressin antagonism, and renin inhibition. Finally, digitalis glycosides may be considered neurohormonal modulators in addition to being positive inotropes. Heart failure is a complex condition that involves many organs and systems besides the heart. Polypharmacy tailored to the individual is mandatory. It is thus necessary to investigate approaches to the modulation of neurohormonal activation beyond ACE inhibition.

Angiotensin Receptor Antagonists↗

PubMed2006

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease.

BACKGROUND: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. AIM: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. PATIENTS: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. METHODS: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. RESULTS: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations >11,450 pmol/8 x 10(8) red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). CONCLUSIONS: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

Adolescent↗

PubMed1994

Is ambient ethene a cancer risk factor?

Ethene is, on a molar basis, a major urban air pollutant. It has been shown beyond doubt that a fraction of inhaled ethene is metabolized in mammals (including humans) via ethylene oxide, an electrophilic reagent that has been shown to be mutagenic and carcinogenic. To the extent that the linearity hypothesis for dose-response relationships at low levels is accepted, exposure to ethene is therefore expected to lead to a risk increment. In order to judge whether ethene as a single compound should be considered a risk factor, it has to be evaluated whether this risk increment is negligibly small or of concern to individuals or societies. The magnitude of the cancer risk from ethene cannot be inferred from animal experiments. Because of saturation of the metabolism of ethene, sufficient statistical power cannot be attained in long-term animal tests with about 100 animals per dose. By application of the radiation-dose equivalent of the unit of target dose of ethylene oxide and using the best (although still uncertain) value for the conversion factor (about 5%), exposure to 10 ppb ethene--a level occurring in urban areas--is expected to lead to a lifetime risk of cancer death amounting to approximately 70 per 100,000. According to a recent estimate the average exposure in Sweden to ethene is some six times lower. These figures are uncertain by a factor of at least three. They indicate ethene to be a risk factor of concern.

Air Pollutants↗

PubMed2005

ACE inhibitors in heart failure: what more do we need to know?

ACE inhibitors have significantly decreased cardiovascular mortality, myocardial infarction (MI), and hospitalizations for heart failure (HF) in patients with asymptomatic or symptomatic left ventricular (LV) systolic dysfunction. Furthermore, the extended 12-year study of the SOLVD (Studies Of Left Ventricular Dysfunction) Prevention and Treatment trials (X-SOLVD) demonstrated a significant benefit with a reduction of cumulative all-cause death compared with placebo (50.9% vs 56.4%) [hazard ratio (HR) 0.86; 95% CI 0.79, 0.93; p < 0.001]. The survival benefits and significant reductions in cardiovascular morbidity related to treatment with ACE inhibitors are likely achieved by titrating the dose of ACE inhibitors to the target dose achieved in clinical trials. Although the ATLAS (Assessment of Treatment with Lisinopril And Survival) study, which randomly allocated HF patients to low- or high-dose lisinopril, showed no significant difference between groups for the primary outcome of all-cause mortality (HR 0.92; 95% CI 0.82, 1.03), the predetermined secondary combined outcome of all-cause mortality and HF hospitalization was reduced by 15% for the patients receiving high-dose lisinopril compared with low-dose (p < 0.001) with a 24% reduction in HF hospitalization (p = 0.002). Despite the use of ACE inhibitors, blockade of the renin angiotensin aldosterone system (RAAS) remains incomplete, with evidence of continued production of angiotensin II by non-ACE-dependent pathways. The safety and potential benefits of angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) in patients with impaired systolic function have been assessed in moderate to large clinical trials. In patients with impaired LV systolic function and HF, combination therapy with ARBs with recommended HF therapy including ACE inhibitors in patients who remain symptomatic may be considered for its morbidity benefit. Based on the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity)-Added data, candesartan cilexetil in addition to standard HF therapy results in a further reduction of cardiovascular mortality. Close monitoring of renal function and serum potassium levels is needed in this setting. The VALIANT (VALsartan In Acute myocardial iNfarction Trial) results suggest that valsartan is as effective as captopril in patients following an acute MI with HF and/or LV systolic dysfunction and may be used as an alternative treatment in ACE inhibitor-intolerant patients. There was no survival benefit with valsartan-captopril combination compared with captopril alone in this trial. Despite these results, ACE inhibitors remain the first-choice therapeutic agent in post-MI patients, and ARBs can be used in patients with clear intolerance. Although the use of ACE inhibitors may be appealing in patients with HF and preserved LV systolic function, there is currently no evidence from large clinical trials to support this.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

ACE inhibitors in pediatric patients with heart failure.

This article reviews reports of ACE inhibitor use in pediatric heart failure and summarizes the present implications for clinical practice. Captopril, enalapril, and cilazapril are orally active ACE inhibitors, and widely used in pediatric cardiology, although more than ten other ACE inhibitors have been applied clinically in adults. Effects of ACE inhibitors on the renin-angiotensin-aldosterone system in pediatric patients are similar to those in adults. ACE inhibitors lower aortic pressure and systemic vascular resistance, do not affect pulmonary vascular resistance significantly, and lower left atrial and right atrial pressures in pediatric patients with heart failure. In infants with a large ventricular septal defect and pulmonary hypertension, ACE inhibitors decrease left-to-right shunt in those infants with elevated systemic vascular resistance. ACE inhibitors induce a small increase in left ventricular ejection fraction, left ventricular fractional shortening, and systemic blood flow in children with left ventricular dysfunction, mitral regurgitation, and aortic regurgitation. These beneficial effects usually persist long term without the development of tolerance. Therapeutic trials of ACE inhibitors have been reported in children with heart failure and divergent hemodynamics, including myocardial dysfunction, left-to-right shunt, such as large ventricular septal defect and pulmonary hypertension, aortic or mitral regurgitation, and Fontan circulation. Hypotension and renal failure usually occur within 5 days after starting ACE inhibition or increasing the dose and, in most cases, recovery is seen after reduction or cessation of the drug. With all ACE inhibitors, smaller doses are administered initially to prevent excessive hypotension, and doses are increased gradually to the target dose. Captopril is administered orally, usually every 8 hours. Daily doses range from 0.3 to 1.5 mg/kg in children. Enalapril is administered orally, once or twice a day, and daily doses range from 0.1 to 0.5 mg/kg. Enalaprilat is administered intravenously, one to three times a day, in doses ranging from 0.01 to 0.05 mg/kg/dose. For the treatment of chronic heart failure in children, ACE inhibitors are essential along with other medications including diuretics, digoxin, and beta-blockers (beta-adrenoceptor antagonists).

Adolescent↗

PubMed1999

A four-part regimen for clinical heart failure.

Combination therapy with a diuretic, digoxin, ACE inhibitor, and beta-blocker can help patients with heart failure caused by severe systolic dysfunction feel better and live longer. Especially with ACE inhibitors and beta-blockers, the key to success is starting at low doses and titrating carefully to proven target doses. The demanding complexity of the four-drug regimen is well worth the results.

Adrenergic beta-Antagonists↗

PubMed1997

[Dose distributions of linac-based radiosurgery for pineal region mass].

The doses of linac convergent-beam irradiations to pineal region were measured in an anthropomorphic phantom. The feasibility of a linac accelerator as a radiosurgery tool to treat small sized intracranial masses was evaluated. The influences of some irradiation parameters on the dose distributions were discussed. Linac-based radiosurgery can result in dose distributions similar to those achieved by gamma knife, so it is another safe and effective treatment technique of neurosurgery. The smaller the aperture is and the greater the irradiation arc travel is, the larger the dose gradient will be and the better the dose distribution will be. The maximum target doses are dependent greatly upon the collimater aperture. The appropriate irradiation arc travel and margin isodose were also discussed.

Brain Neoplasms↗

PubMed1986

Analysis of dose intensity for chemotherapy in early (stage II) and advanced breast cancer.

In chemotherapy of advanced breast cancer, the dose intensities of regimens containing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) and cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) correlate with remission rate. The correlation is even better if dose intensity is calculated from doses actually given instead of from targeted doses. Also, in adjuvant chemotherapy of stage II breast cancer, the dose intensities of CMF-containing regimens correlate with relapse-free survival. The adjuvant trials analyzed included studies containing only 1 or 2 of C, M, or F or with L-phenylalanine mustard (melphalan) instead of C. Three-year relapse-free survival was clearly related to dose intensity whether the analysis was of trials containing all 4 prognostic groups [women less than 50 yr with 1-3 and greater than 3 positive nodes; and those greater than or equal to 50 yr with 1-3 and greater than 3 positive nodes (P less than .00001)] or of trials in which each of these 4 groups were analyzed separately (P less than .005). In multivariate analysis, dose intensity correlated with relapse-free survival (P less than .00001), independent of the number of positive nodes or menopausal status. Randomized trials will be required before we can determine if prospective increases of dose intensity will improve outcome of chemotherapy in breast cancer.

Adult↗