Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dose reduction”

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

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

At least 433 records · Page 24Linked to original sources
PubMed2000

Clinical experience with routine diode dosimetry for electron beam radiotherapy.

PURPOSE: Electron beam radiotherapy is frequently administered based on clinical setups without formal treatment planning. We felt, therefore, that it was important to monitor electron beam treatments by in vivo dosimetry to prevent errors in treatment delivery. In this study, we present our clinical experience with patient dose verification using electron diodes and quantitatively assess the dose perturbations caused by the diodes during electron beam radiotherapy. METHODS AND MATERIALS: A commercial diode dosimeter was used for the in vivo dose measurements. During patient dosimetry, the patients were set up as usual by the therapists. Before treatment, a diode was placed on the patient's skin surface and secured with hypoallergenic tape. The patient was then treated and the diode response registered and stored in the patient radiotherapy system database via our in-house software. A customized patient in vivo dosimetry report showing patient details, expected and measured dose, and percent difference was then generated and printed for analysis and record keeping. We studied the perturbation of electron beams by diodes using film dosimetry. Beam profiles at the 90% prescription isodose depths were obtained with and without the diode on the beam central axis, for 6-20 MeV electron beams and applicator/insert sizes ranging from a 3-cm diameter circular field to a 25 x 25 cm open field. RESULTS: In vivo dose measurements on 360 patients resulted in the following ranges of deviations from the expected dose at the various anatomic sites: Breast (222 patients) -20.3 to +23.5% (median deviation 0%); Head and Neck (63 patients) -21.5 to +14.8% (median -0.7%); Other sites (75 patients) -17.6 to +18.8% (median +0.5%). Routine diode dosimetry during the first treatment on 360 patients (460 treatment sites) resulted in 11.5% of the measurements outside our acceptable +/-6% dose deviation window. Only 3.7% of the total measurements were outside +/-10% dose deviation. Detailed investigations revealed that the dose discrepancies, overwhelmingly, were due to inaccurate diode orientation and positioning, especially in the regions with rapidly changing contours and/or sloping surfaces. The presence of a diode in the treatment field was found, in some cases, to cause significant dose reduction, most noticeable with smaller fields and lower energy beams. The reduction in dose ranged from 16% (for a 6 MeV beam and a 3 cm diameter circular field) to 4% (for a 12 MeV beam and a 10 x 10 cm field). CONCLUSIONS: Diode dosimetry was found to be convenient and valuable for verifying in real time the dose delivery accuracy of electron beam treatments, but with some caveats. When treating a small field by low energy electrons, frequent use of diodes is undesirable, because it might result in appreciable reduction of dose to the target volume.

Calibration↗
PubMed2006

Usefulness of saline pushing in reduction of contrast material dose in abdominal CT: evaluation of time-density curve for the aorta, portal vein and liver.

The effects of saline pushing after contrast material injection were investigated as well as the possibility for this technique to reduce contrast material doses in liver CT examinations. 52 patients were divided randomly into three groups: 100 ml of contrast material (300 mg I ml(-1)) only (A; n = 19), 100 ml of contrast material pushed with 50 ml of saline solution (B; n = 17), and 85 ml of contrast material pushed with 50 ml of saline solution (C; n = 16). Single-level images were obtained at the level of the main portal vein after the initiation of contrast material injection. There were no significant differences in the mean peak enhancement values (PE) and the mean time to peak enhancement values (TPE) of the aorta between the three groups. The mean PE of the portal vein in group B increased 21 HU over that in group A (p<0.05), and there was no significant difference between groups A and C. The mean PE of the liver in group B increased 7 HU over that in group A (p<0.05), and there was no significant difference between groups A and C. The mean TPE of the portal vein was shorter by 4 s (p<0.05), and that of the liver was shorter by 5 s (p<0.05) in group C compared with those in group A. In conclusion, saline pushing increases the enhancement values of the portal vein and liver, and allows a contrast material dose reduction of 15 ml without decreasing hepatic and vascular enhancement at adequate scan timing.

Adult↗
PubMed1992

Maintenance with low-dose cytarabine for acute myeloid leukemia in complete remission.

Thirty-four patients with acute myeloid leukemia (AML) in complete remission (CR), 30 of them aged over 60, received maintenance therapy scheduling four courses of low-dose cytarabine (LDA) 20 mg/m2/day in two subcutaneous injections for 3 weeks every 6 weeks. Each course was stopped when hematologic toxicity occurred, and doses of LDA were subsequently reduced by 50% for the following courses. During the first course of LDA, 15 patients needed blood and four patients platelet transfusions. Overall, 28 patients received four courses of LDA: 11 did not require any dose reduction, while 14 required one dose reduction and three needed two successive dose reductions. Two patients were hospitalized during maintenance. Median disease-free survival (DFS) is 308 days, with 16% of patients surviving at 5 years. Seven patients relapsed during the 168 days of maintenance, while ten of the 27 patients remaining at risk on day 169 relapsed during the 168 days following maintenance. We conclude that in AML in CR, the maximal dose of LDA tolerated by ambulatory patients is 10 mg/m2/day for 3 weeks. LDA seemed to delay relapse; however, precise assessment of the efficacy of this approach would require a randomized trial.

Acute Disease↗
PubMed2004

[Incidence of haemolytic anaemia during combination therapy of chronic hepatitis C with interferon alpha-2b and ribavirin].

OBJECTIVE: Analysis of incidence of haemolytic anaemia during INF-alpha + ribavirin (RBV) treatment of chronic hepatitis C (CHC). MATERIAL AND METHODS: 95 patients (M=64, F=31, mean age: 42.5 +/- 11.9) with CHC. All patients received IFN-alpha 3 MU three times a week and 1000-1200 mg of RBV daily. Basic haematological and biochemical parameters were checked. HCV-RNA (Cobas Amplicor, Roche) was checked before and after 6 months of therapy. RESULTS: After the first month of treatment a reduction of haemoglobin level occurred at 30% patients (not always characteristic for anaemia), an increase of the total bilirubin was observed in 16.8%, ferrum in 15.8%, while that of lactate dehydrogenase only in 22.1%. 37% of the patients required a reduction of ribavirin doses. No patient had treatment stopped because of side effects. CONCLUSIONS: Lower HGB, RBC, WBC, HCT and PLT levels and raised total and unconjugated bilirubin levels were the most frequent changes observed during the combined antiviral treatment. Improvement of haematological and biochemical parameters most often occurs spontaneously or after RBV dose reduction. Presence of haemolytic anaemia does not require stopping of RBV treatment, but only RBV dose reduction. At about 2/3 of patients who start therapy with interferon and RBV treatment has to be continued up to 48 weeks.

Adult↗
PubMed2004

Pre-transplant inosine monophosphate dehydrogenase activity is associated with clinical outcome after renal transplantation.

UNLABELLED: Mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase (IMPDH) activity, is usually administered as a standard dose of 1 g b.i.d. after renal transplantation. Because MMF dose reductions are associated with inferior outcome, we investigated pre-transplant IMPDH activity, MMF dose reductions and outcome. IMPDH activity was determined in isolated peripheral mononuclear cells immediately prior to renal transplantation. We observed considerable inter-individual variability in pre-transplant IMPDH activity (9.35 +/- 4.22 nmol/mg/h). Thirty of 48 patients (62.5%) with standard MMF dose (1 g b.i.d.) had dose reductions within 3 years post-transplant; these patients also had significantly lower IMPDH activity. The area under the receiver-operating characteristics curve (AUC-ROC) for prediction of dose reduction within 6 months post-transplant was 0.75 (95% CI, 0.61-0.89; p < 0.004). IMPDH activity above the cut-off value, MMF dose reduction and age of recipient were significant contributors for the occurrence of acute rejection in the multivariate logistic regression. Patients with high IMPDH activity and MMF dose reduction had the highest rejection rate (81.8% vs. 36.4%; p < 0.01). CONCLUSION: Patients with low IMPDH activity experienced more complications of MMF therapy. High pre-transplant IMPDH activity and MMF dose reductions were associated with rejection. Determination of IMPDH activity prior to transplantation may help to improve MMF therapy after renal transplantation.

Area Under Curve↗
PubMed1996

A pilot trial of continuous infusion 5-fluorouracil with levamisole for adjuvant therapy of colon cancer.

The relatively high response rate demonstrated with the use of continuous infusion 5-Fluorouracil (CIFU) 200 to 300 mg/m2 per day in disseminated colon cancer is the rationale behind a NCI-sponsored intergroup trial (INT 0153) for postoperative adjuvant therapy of stage III colon cancer. Because CIFU necessitates a significant reduction in the dose of the modulator leucovorin compared with bolus 5-FU, a pilot study of continuous infusion 5-FU in several doses with levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of this dose intensive schedule. CIFU, scheduled as two 12-week cycles, was administered at 250 mg/m2 per day. Pending toxicity at the initial dose, CIFU was to be escalated (300 mg/m2) or de-escalated (200 mg/m2). All but one patient entered on this trial completed 24 weeks of adjuvant CIFU+levamisole. Eight patients (57%) completed 24 weeks of therapy with the 2-week scheduled break. One of these 8 patients required a dose reduction without interrupting the schedule. Six patients had toxicity from the CIFU, which obliged us to interrupt the schedule. Limiting toxicities were stomatitis and hand-foot syndrome. No dose-limiting hematologic toxicity was encountered. Three patients (21%) had catheter problems that required replacement. These data suggest that up to 30% of patients started on this regimen may require dose reduction, shorter infusion courses with rest breaks, or both to complete 24 weeks of adjuvant treatment in order to achieve desired dose intensity.

Adult↗
PubMed1998

Dose rate correction in medium dose rate brachytherapy for carcinoma cervix.

PURPOSE: To establish the magnitude of brachytherapy dose reduction required for stage IIB and III carcinoma cervix patients treated by external radiation and medium dose rate (MDR) brachytherapy at a dose rate of 220+/-10 cGy/h at point A. MATERIALS AND METHODS: In study-I, at the time of MDR brachytherapy application at a dose rate of 220+/-10 cGy/h at point A, patients received either 3060 cGy, a 12.5% dose reduction (MDR-12.5), or 2450 cGy, a 30% dose reduction (MDR-30), to point A and they were compared to a group of previously treated LDR patients who received 3500 cGy to point A at a dose rate of 55-65 cGy/h. Study-II was a prospective randomized trial and patients received either 2450 cGy, a 30% dose reduction (MDR-II (30)) or 2800 cGy, a 20% dose reduction (MDR-II (20)), at point A. Patients were evaluated for local control of disease and morbidity. RESULTS: In study-I the 5-year actuarial local control rate in the MDR-30 and MDR-12.5 groups was 71.7+/-10% and 70.5+/-10%, respectively, compared to 63.4+/-10% in the LDR group. However, the actuarial morbidity (all grades) in the MDR-12.5 group was 58.5+/-14% as against 34.9+/-9% in the LDR group (P < 0.05). Similarly, the grade III and IV morbidity also in the MDR-12.5 group was 12.5+/-9% as against 5.3+/-5% in the LDR group (P < 0.05). No statistically significant difference in morbidity was seen between the MDR-30 and LDR groups. In study-II the 3-year actuarial local control rate in the MDR-II (30) and MDR-II (20) groups was 66.6+/-10% and 74.8+/-9%, respectively. There was a significant correlation between the rectal BED received and the percentage of patients developing rectal morbidity. Only 10% of patients receiving a rectal BED of (100 < 120) Gy3 developed complication as against 62.5% of those receiving a rectal BED of (140 < 160) Gy3 (chi2 = 46.43; P < 0.001). CONCLUSION: We suggest that at a dose rate of 220+/-10 cGy/h at point A the brachytherapy dose reduction factor should be around 30%, as suggested by radiobiological data, to keep the morbidity as low as possible without compromising the local control rates.

Brachytherapy↗
PubMed1992

An investigation into the effect of protective devices on the dose to radiosensitive organs in the head and neck.

A series of experiments were performed to determine the dose reduction afforded to radiosensitive organs in the head and neck by various protective devices. These included spectacles with plastic, standard glass, photochromic and lead-glass lenses, a thyroid collar and a lead-acrylic face mask. The measurements were performed using an anthropomorphic phantom loaded with lithium fluoride thermoluminescent dosemeters, in conditions realistic of clinical practice. Irradiations were performed using scattered radiation produced by a pelvic phantom, for X-ray beams generated at 80 kVp and 110 KVp. It was found that the reduction in dose to the lens of the eye ranged between 0% and 97%, whilst the dose to the thyroid and oesophagus was reduced by between 76% and 97%, and was dependent on the protective device and tube potential employed. A reduction in brain dose of up to 81% was also measured, for the lead-acrylic face mask. Also presented is the ratio of organ dose to dose to the bridge of the nose for thyroid, oesophagus, brain and sinuses, as measured for the case of no head or neck protection.

Brain↗
PubMed1985

[Reduction of patient dose with maximum assurance of image quality].

Four methods of reducing the patient dose are reviewed. Without doubt, the patient dose can be considerably reduced by relatively simple means: With rare-earth screens by a factor of 2-4 compared with a CaWO4 universal screen (1 mR) and in some cases by a factor of 1.5-2 with prefiltration. A more complicated and expensive method is the 100 mm spotfilm technique. This permits a dose rate reduction by a factor of 10 compared with a CaWO4 universal screen or by a factor of 5 compared with a universal system with rare-earth screens. In the wide-ranging field of digital radiography, the possibilities of dose reductions by means of digital processing of conventional film screen exposures are investigated.

Absorption↗
PubMed1990

Successful treatment of hairy cell leukemia with beta-ser interferon.

Twelve patients with hairy cell leukemia underwent treatment with beta-ser interferon, a type I interferon with potent antiproliferative activity. Ten of the 12 patients had had prior therapy and the median time from diagnosis to initiation of treatment was 8.5 months (range 1 month to 18 years). Bone marrow involvement ranged from 90-100% hairy cells. Beta-ser interferon was administered as an intravenous injection of 90 million units per dose, three times weekly. Dose reductions were by dose and by frequency in individual patients. Ten of 12 patients (83%) responded, including 7 complete (CR) and 3 partial (PR) responses. The median time to at least PR was 6 months and the median time to CR was 12 months. The median duration of overall response (PR + CR or PR) is 31+ months (range 26(+)-40+ months). Of the 6 patients who underwent dose reductions due to toxicity or poor tolerance, 4 CR patients reverted to PR, and 2 PR patients have increased the number of hairy cells in the marrow, while maintaining normal peripheral blood counts. One each of these has regained CR and PR status after an increase in dose.

Adult↗
PubMed2002

G-CSF as prophylaxis of febrile neutropenia in SCLC.

OBJECTIVES: In 1991, small cell lung cancer (SCLC) was reported as the first tumour type where colony stimulating factor (CSF) support was clinically effective. We reviewed 13 health services research studies that addressed CSF use as supportive care for SCLC. METHODS: Findings from American Society of Clinical Oncology (ASCO) membership surveys, patterns of care studies, ASCO evidence-based guidelines and cost-effectiveness studies for CSF use were reviewed. RESULTS: For primary prophylaxis for SCLC, ASCO CSF clinical guidelines clearly do not support granulocyte (G)-CSF use. Cost-effectiveness models indicate that CSF use in this setting is associated with as much as US$1900 incremental patient care costs per cycle given an 18% febrile neutropenia rate. ASCO membership surveys found that < 10% of respondents supported CSF as primary prophylaxis while a patterns-of-care study found 55% use. In the secondary prophylaxis setting, ASCO CSF guidelines in 1994, 1996 and 1997 were equally supportive of CSF use versus dose reduction but dose-reduction was considered the preferred option in 2000. Over half of the ASCO member respondents in 1994 and in 1997 supported G-CSF use; cost-effectiveness models indicated that CSF use incurred an additional US$144 and 277 per cycle and the patterns of care study found 27% use of CSF in the community practice setting. CONCLUSIONS: In 2002, the findings of a decade of health services studies have shifted towards not being supportive of CSF use for primary or secondary prophylaxis for SCLC patients.

Carcinoma, Small Cell↗
PubMed1982

Prevention of propranolol withdrawal mechanism by prolonged small dose propranolol schedule.

Abrupt withdrawal of propranolol may be followed by a "propranolol withdrawal syndrome "due, at least in part, to enhanced beta adrenergic sensitivity. Tapering propranolol dosage is frequently used in the hope of preventing adverse withdrawal events but the success of such a maneuver has not been shown. The rationale for the dose tapering schedule in this study was based on earlier observations after abrupt withdrawal of propranolol. Nine hypertensive patients were gradually withdrawn from long-term propranolol therapy, either by serial dose reduction for 6 to 9 days (n = 3) or by reduction to a prolonged small dose (30 mg daily) for 2 weeks before complete withdrawal (n = 6). During dose reduction of propranolol and for 2 additional weeks of placebo therapy, serial measurements were made of cardiac sensitivity to isoproterenol, heart rate at rest, blood pressure, plasma catecholamines, serum thyroxine (T4) and triiodothyronine (T3) and symptoms. Serial dose reduction decreased but did not prevent cardiac hypersensitivity in two of three patients. The prolonged small dose therapy largely prevented cardiac hypersensitivity and overshoot in heart rate, blood pressure and plasma catecholamines and symptoms. Serum T4 decreased significantly and T3 tended to increase during and after prolonged small dose treatment. These results indicate that prolonged administration of small dose propranolol before complete withdrawal in hypertensive patients prevents enhanced cardiac beta adrenergic sensitivity and other adverse events.

Adult↗
PubMed1996

[The efficacy of lead shielding in patient dosage reduction in computed tomography].

PURPOSE: Investigation of the efficacy of lead apron, testis capsule and thyroid collar for dose reduction in uterus, ovaries, testes and thyroid gland in computed tomography examinations. METHODS: At an Alderson-Rando phantom dose of uterus, ovaries, testes and thyroid gland was measured with thermoluminescent dose meters. CT of the upper abdomen, the whole abdomen and the skull were simulated without and with lead shielding. As lead shielding, a lead apron was attached around the pelvis of the phantom in case of CT of the upper abdomen, a testis capsule was used in CT of the whole abdomen and a thyroid collar in CT of the skull. RESULTS: In CT of the upper abdomen the lead apron did not lead to any recognisable dose reduction in uterus and ovaries. In CT of the whole abdomen the testis capsule led to a dose reduction in testes of 95% (1.39 mSv) and in CT of the skull the thyroid collar to a dose reduction in thyroid gland of 23% (0.19 mSv). CONCLUSIONS: In abdominal CT examinations the testis capsule is an important instrument to reduce the dose of the testes whereas the lead apron is not appropriate for a dose reduction in the uterus and ovaries. In CT of the skull the thyroid collar can remarkably reduce the scattered radiation exposure of the thyroid gland and should be recommended.

Female↗
PubMed1994

Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

PURPOSE: A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS: Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.

Adult↗
PubMed1993

Effects of dose limits reduction on the Argentine nuclear power plants.

Occupational doses are evaluated in different stages of the fuel cycle and in the operation of nuclear power plants. Trends in individual dose distribution and collective doses are analyzed. The most contributive working conditions to collective dose are identified and the implications of dose limit reduction recommended by the ICRP in 1990 are assessed. It is concluded that no relevant difficulties should appear in accomplishing the new recommendations except for implementation at Atucha I, a nuclear power plant designed in the 1960s. Some options to reduce individual and collective doses in this plant are analyzed. The change of fuel channels by new ones free from cobalt is essential to get effective improvement of occupational exposures.

Argentina↗
PubMed2006

Cost-effectiveness of growth factors during hepatitis C anti-viral therapy.

BACKGROUND: Although the current standard of care for controlling anaemia and neutropenia during anti-viral therapy for hepatitis C is to use dose reduction of ribavirin and pegylated interferon, respectively, erythropoietin and granulocyte colony-stimulating factor are now being advocated as alternatives to dose reduction. AIM: To determine the cost-effectiveness of erythropoietin and granulocyte colony-stimulating factor as an alternative to anti-viral dose reduction during antihepatitis C therapy. METHODS: Decision analysis was used to assess cost-effectiveness by estimating the cost of using a growth factor per quality-adjusted life-year gained. RESULTS: Under baseline assumptions, the cost per quality-adjusted life-year of using growth factors ranged from 16,247 US dollars for genotype 1 with neutropenia to 145,468 US dollars for genotype 2/3 patients with anaemia. These findings are sensitive to the relationship between dose reduction and sustained virological response. CONCLUSIONS: Based upon our findings and the varying strength of the evidence for a relationship between dose reduction and sustained virological response: granulocyte colony-stimulating factor may be cost-effective for genotype 1 patients; erythropoietin is probably not cost-effective for genotype 2/3 patients; no conclusion can be reached regarding the cost-effectiveness of erythropoietin for genotype 1 patients or granulocyte colony-stimulating factor for genotype 2/3 patients. Randomized trials are needed to firmly establish the relationship between dose reduction and sustained virological response.

Antiviral Agents↗
PubMed1992

Buprenorphine: an alternative to methadone for heroin dependence treatment.

Eighty-five heroin addicts who were unwilling to receive methadone maintenance or enter therapeutic communities were assessed, single-blind, for the lowest sublingual dose of buprenorphine that blocked heroin craving (8.0 mg max). All doses were administered daily under observation. After maintenance for 4 to 12 weeks, abstinent subjects (confirmed by urine drug screens) entered a double-blind discontinuation trial and were randomly assigned to receive dose reductions (10% twice weekly for 5 weeks to zero dose, then placebo for 2 weeks) or a stable dose for 7 weeks. Subjects were terminated from discontinuation if heroin was used or they had increased craving/symptoms. Subjects completed the trial if they did not use heroin and had no increase in craving/symptoms. A wide dose range (1.5-8.0 mg/day) was effective in reducing heroin craving and use. Of 73 subjects who received buprenorphine for 4 to 52 weeks, 40 had no prior treatment, despite high levels (mean $/day heroin = 70.5 +/- 94.7) and many years (mean years = 10.7 +/- 8.6) of dependence. Subjects who received dose reductions developed abstinence symptoms, low energy most commonly, associated with drug-seeking behavior. Discontinuation trial outcome (n = 51) shows a highly significant difference between 29 subjects who received dose reductions (28 terminated, 1 completed) and 22 subjects who received no dose reductions (3 terminated; 19 completed) (chi-square = 36.08; p less than .00001). The findings suggest that buprenorphine could be an important medication for reducing demand for heroin by many heroin addicts who remain outside the present health-care system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2000

Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease.

Gaucher disease is caused by a deficiency of beta-glucocerebrosidase activity. The optimum dose and frequency of enzyme replacement therapy for Gaucher patients have not been determined. We set to compare the therapeutic effects of initiating treatment with macrophage-targeted glucocerebrosidase at a high dose followed by progressive dose reductions with that produced by initial treatment at a low dose in patients with type I Gaucher disease. The study included two parts: (i) Twelve patients received every 2 weeks enzyme replacement therapy at 60 IU/kg body wt for 24 months followed by sequential dose reduction every 6 months to 30 and then to 15 IU/kg body wt. (ii) Thirty-two patients received enzyme replacement therapy at 10 IU/kg every 2 weeks for 12 months. Hematologic parameters and liver and spleen volume were monitored in all patients. All patients had intact spleens. In patients who were started on high-dose enzyme replacement therapy, hemoglobin, acid phosphatase, and organ volume improved or remained unchanged at the end of each dose reduction. Platelet count decreased significantly when the dose of enzyme was reduced from 30 to 15 IU/kg body wt. Initiation of therapy at a low dose led to a significant improvement in all measured parameters at the end of 1 year. We conclude that the minimal effective dose for the nonskeletal manifestations of Gaucher disease can be achieved either by initiating enzyme replacement therapy with a high dose followed by a stepwise dose reduction or by starting treatment at the minimal dose. High dose provides a faster clinical response and should be considered for patients with more aggressive disease. The therapeutic threshold for macrophage-targeted glucocerebrosidase appears to be 10-15 IU/kg body wt every 2 weeks.

Adolescent↗