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PubMed2000

Chest radiography with a large-area detector based on cesium-iodide/amorphous-silicon technology: image quality and dose requirement in comparison with an asymmetric screen-film system.

The purpose of this study was to evaluate a large-area, flat-panel X-ray detector, which uses cesium-iodide (CsI) and amorphous silicon (a-Si). Conventional images were compared with digital images acquired with equal dose (2.5 microGy) and with 50% dose reduction. Fifteen consecutive patients were studied prospectively using an asymmetric screen-film system (detector dose, 2.5 microGy). Digital images were taken from the same patients in a posteroanterior view with detector doses of 2.5 and 1.25 microGy, respectively. The CsI/a-Si active-matrix imager had a panel-size of 43 x 43 cm, a matrix of 3 x 3k, and a pixel-pitch of 143 microm. Hard copies were presented in a random order to eight independent observers, who rated image quality according to six subjective quality criteria. Statistical significance of differences was evaluated with Student's t test for paired samples (confidence level, 95%). Digital radiographs with 2.5 and 1.25 microGy were superior to conventional images regarding all quality criteria. Statistically significant differences were observed for five of six criteria at a detector dose of 2.5 microGy and for only one quality feature at 1.25 microGy. Flat-panel digital imagers based on CsI/a-Si technique have the potential to replace conventional systems and might allow a reduction of radiation dose by 50% without loss of image quality.

Adult↗
PubMed2000

Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels.

BACKGROUND: The optimal risperidone dosing strategy for acute schizophrenia requires elucidation. Furthermore, plasma levels of risperidone and its active metabolite (9-hydroxyrisperidone) at a given dose vary greatly among different individuals. For patients who metabolize risperidone slowly, a medium dose results in excessively high plasma levels, which might be related to adverse events and perhaps poor response. We thus investigated whether dose reduction to diminish adverse reactions associated with ordinary risperidone doses could still yield efficacy for acutely exacerbated schizophrenia. METHOD: Thirty-one newly hospitalized Chinese patients with acute exacerbation of schizophrenia (DSM-IV) entered this prospective, 6-week open trial. Risperidone doses were titrated to 6 mg/day (if tolerable) over 3 days, but were lowered thereafter if side effects appeared. Efficacy and side effect assessments were conducted on days 0, 4, 14, 28, and 42. Endpoint steady-state plasma levels of risperidone and 9-hydroxyrisperidone were analyzed by high performance liquid chromatography with ultraviolet detection. RESULTS: Thirty patients completed the trial. Of them, 17 tolerated the 6-mg target dose well, while the other 13 received lower final doses (mean +/- SD = 3.6 +/- 0.9 mg, p = .0001) for curtailing treatment-emergent side effects. At endpoint, 92.3% of the 13 low-dose individuals responded to treatment (20% or more reduction in the total Positive and Negative Syndrome Scale score), compared with 52.9% of the 17 high-dose subjects (p < .05). No significant between-group differences were revealed in other minor efficacy measures. Of note, endpoint plasma levels of the active moiety (risperidone plus 9-hydroxyrisperidone) were similar between the low- and high-dose groups (40.4 +/- 31.1 ng/mL vs. 49.7 +/- 13.4 ng/mL, NS). CONCLUSION: The results of this preliminary trial suggest that up to 6 mg of risperidone is efficacious in treating patients with acute exacerbation of schizophrenia. Nearly 60% of the patients could tolerate a 6-mg dose. For the other 40%, reducing dosages to 3.6 +/- 0.9 mg for relieving side effects still yielded efficacy. The 2 dose groups were comparable in the endpoint steady-state plasma drug concentrations.

Acute Disease↗
PubMed1999

Regional and temporal expression of the peripheral benzodiazepine receptor in MPTP neurotoxicity.

We used the dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to evaluate the sensitivity and specificity of the peripheral benzodiazepine receptor (PBR) as a biomarker of chemical-induced neurotoxicity. Receptor autoradiography of [3H]-PK11195, a PBR selective ligand, indicated dose-dependent increases throughout the nigrostriatal dopaminergic system as early as 24 h after MPTP administration (10-80 mg/kg), which persisted for at least 21 days. The binding of [3H]-PK11195 was increased as much as 98% in the corpus striatum and 114% in the substantia nigra, following MPTP exposure. The integrity of nigrostriatal dopaminergic terminals in the corpus striatum was assessed by measuring high affinity dopamine transporter (DAT) levels and dopamine content. DAT levels were measured by [3H]-WIN 35,428 autoradiography, and dopamine content decreased with increasing MPTP dose. Reductions of both indices of dopaminergic terminal integrity correlated with increased levels of [3H]-PK11195-binding in the striatum (r2 = 0.84 for DAT and 0.93 for dopamine content). Tyrosine hydroxylase (TH) immunohistochemistry demonstrated dose-dependent reductions of dopaminergic neurons in the substantia nigra pars compacta, with a 67% loss measured 7 days after treatment with 80 mg/kg MPTP. The loss of TH-positive neurons was correlated (r2 = 0.95) with increased levels of [3H]-PK11195 binding in the substantia nigra. These findings demonstrate that the PBR is both sensitive and specific for identifying brain regions involved in MPTP neurotoxicity.

Animals↗
PubMed2006

Tube current reduction in pediatric non-ECG-gated heart CT by combined tube current modulation.

BACKGROUND: Dose reduction by combined tube current modulation has not been evaluated in pediatric low-dose CT. OBJECTIVE: This study was performed to evaluate tube current reduction in non-ECG-gated heart CT angiography in children by combined tube current modulation, and to assess the effects of body weight, age, sex, and scan direction on tube current reduction. MATERIALS AND METHODS: From September 2004 to January 2005, non-ECG-gated heart CT examinations were performed with combined tube current modulation in 50 children (median age 1 year, range 1 month to 16 years; M/F 29/21) with congenital heart disease. Sixteen-slice spiral CT studies were obtained using a weight-based low-dose protocol (80 kVp, 50-160 effective mA). CT scans were obtained in the craniocaudal direction when leg veins (n=36) were used for IV injection of contrast agent and in the caudocranial direction when arm veins (n=13) were used. In one child who underwent a Fontan operation, both arm and leg veins were used. We calculated tube current reduction by combined tube current modulation and evaluated the effects of body weight, age, sex, and scan technique on tube current reduction. The quality of CT angiography images was visually evaluated by an experienced pediatric radiologist. RESULTS: Overall tube current reduction by combined tube current modulation was 15.8+/-11.1%. The reduction was variable among five body weight groups (9.3+/-7.9% for <4.9 kg, 14.3+/-9.3% for 5.0-9.9 kg, 16.4+/-12.5% for 10.0-19.9 kg, 25.8+/-9.8% for 20.0-39.9 kg, 15.9+/-12.7% for 40.0-59.9 kg) and was significantly different among the five groups (P=0.017). When eight children in the 40.0-59.9-kg group were excluded, age showed a significant positive correlation with tube current reduction (gamma=0.4, P=0.003). There was no significant difference in tube current reduction between boys and girls. Tube current reduction was significantly greater for the caudocranial scan (21.2+/-9.2%) than for the craniocaudal scan (14.2+/-11.3%) (P=0.049). All CT angiography images were of diagnostic quality. CONCLUSIONS: Combined tube current modulation reduced tube current in pediatric non-ECG-gated heart CT by 15.8% without degradation of image quality. With our CT protocol, for body weights up to 39.9 kg, age showed a significant positive correlation with tube current reduction, but there was a lower dose-saving effect in children heavier than 40 kg. Tube current reduction was not affected by sex, but was affected by scan direction.

Adolescent↗
PubMed1981

Evaluation and testing of in vitro labeled technetium Tc-99m red blood cells in two animal models for neonatal RBC volume determinations.

The present study was designed to evaluate the red blood cell (RBC) radiolabeling technique utilizing the short half-lived radionuclide technetium-99m and to compare the results with the well-recognized standard chromium-51 method. The procedure was evaluated in a canine and a newborn lamb model utilizing dual radionuclide labeling and counting techniques. With the express purpose of providing a significant radiation dose reduction, the procedure presented was adapted for utilization in a neonatal patient population. Statistical analysis of the data revealed that there was no significant difference in the radiolabeling efficiency for the two methods (Cr-51, 86.6%; Tc-99m, 92.4%). Assessment of the in vitro stability for technetium-99m RBCs showed that less than a 4% loss of radiolabel from the RBC was seen in a 4-hr time span in the canine model (15 min, 90.5%; 2 hr, 88.9%; 4 hr, 86.6%) when compared to the 15 min equilibrium sample. Evaluation of newborn lamb RBC volumes showed that the technetium-99m RBC volume did not significantly differ from the chromium-51 labeling technique (Cr-51, 24.0 ml/kg; Tc-99m, 23.2 ml/kg). Summarization of the whole-body radiation dose showed that greater than a 30-fold reduction in absorbed dose was achieved in the newborn (Cr-51, 30.0 mrad; Tc-99m, 0.9 mrad). The modified procedure presented for the radiolabeling of the RBC with the short half-lived radionuclide technetium-99m provides a technique comparable to the utilized standard chromium-51 RBC method, yet with a large reduction in absorbed radiation dose. This procedure is presented as a superior technique for the determination of pediatric RBC volumes.

Animals↗
PubMed2004

Analysis of the cardiovascular risk profile in stable kidney transplant recipients after 50% cyclosporine reduction.

BACKGROUND: Long-term use of cyclosporine (CsA) contributes to post-transplant cardiovascular disease (CVD). Hence, a reduction in CsA dosage in kidney transplant recipients (KTR) may improve long-term outcomes. We analyzed the effects of 50% CsA dose reduction on the CVD risk profile in stable KTR. METHOD: Thirty-one KTR on a regimen of CsA, prednisone and mycophenolate mofetil (MMF) were studied. Patients were randomized to either a) continue their previously determined CsA dose (control group, n = 15) or b) lower their CsA dose by 50% (CsA reduction group, n = 16). Renal function, blood pressure, lipid profile, plasma homocysteine (HCY), C-reactive protein (CRP), fibrinogen, and uric acid were compared at baseline and at 6 months. RESULTS: At 6 months, there was a significant improvement in allograft function, systolic blood pressure, number of anti-hypertensive medications and serum uric acid levels in the CsA reduction group. No significant decrease in plasma HCY, CRP, fibrinogen or improvement in lipid profile was found. In contrast, in the Control group, there was a significant increase in HCY, uric acid, and triglycerides. No acute rejection occurred in either group. CONCLUSIONS: A greater reduction in CsA dose could further improve CVD risk profiles, although this may increase the risk of acute or subclinical rejection.

Adult↗
PubMed1998

Neutropenic complications in advanced-stage non-Hodgkin's lymphoma: implications for the use of prophylactic recombinant human granulocyte-colony stimulating factor (G-CSF).

OBJECTIVES: To determine the incidence of neutropenic complications in patients receiving chemotherapy for advanced-stage non-Hodgkin's lymphoma (NHL), to predict which patients are at high risk for neutropenic complications and to develop an economic model for subsequent testing to assess the potential cost-effectiveness of prophylactic treatment with recombinant human granulocyte-colony stimulating factor (G-CSF). DESIGN: Retrospective chart review. PATIENTS: Forty-two patients with advanced-stage NHL treated at the Tom Baker Cancer Centre, Calgary, between Jan. 1, 1992, and Dec. 31, 1993. OUTCOME MEASURES: Neutropenic complications including incidence of febrile neutropenic events, documented infections, and chemotherapy dose delays or dose reductions. RESULTS: Of the 42 patients, 8 (19%) experienced febrile neutropenic events and 18 (43%) required chemotherapy dose modifications (delays or reductions or both) because of neutropenia. Fifteen patients (36%) were identified as being at high risk for neutropenic complications and may have benefited from the administration of prophylactic G-CSF. An economic model developed to assess the potential cost-effectiveness of prophylactic G-CSF therapy estimated that, for high-risk patients, the theoretical incremental cost per life year saved was $3300. CONCLUSIONS: Febrile neutropenia and infection cause significant morbidity and mortality in patients receiving combination chemotherapy for the treatment of advanced-stage NHL. Secondary prophylactic G-CSF therapy has been proven to decrease the incidence of febrile neutropenia and infection in these patients. Considering the reduction in neutropenic complications and resulting increase in chemotherapy dose intensity received by patients on G-CSF, the theoretical incremental cost per life year saved of $3300 with G-CSF therapy is relatively low compared with other medical interventions.

Adult↗
PubMed2003

EORTC Cancer in the Elderly Task Force guidelines for the use of colony-stimulating factors in elderly patients with cancer.

Increasing age is not, in itself, a contraindication to cancer chemotherapy. Myelosuppression, however, a common adverse consequence of the administration of many standard-dose chemotherapy regimens to both young and elderly patients with cancer, increases with age. The risk of development of febrile neutropenia may contribute to a reluctance to administer chemotherapy in the elderly patient population. We conducted a detailed literature search (1992-2002) to derive evidence-based conclusions on the value of prophylactic colony-stimulating factor (CSF) administration in elderly patients receiving chemotherapy. Sufficient evidence allows us to affirm that prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the incidence of chemotherapy-induced neutropenia, febrile neutropenia and infections in elderly patients receiving myelotoxic chemotherapy for non-Hodgkin's lymphoma (NHL), small-cell lung cancer (SCLC) or urothelial tumours. Lack of available trial data does not allow similar conclusions to be drawn for other cancers studied, but it is likely that similar benefits would accrue from the use of prophylactic G-CSF. There is insufficient evidence to extend this recommendation to include the use of granulocyte-macrophage colony-stimulating factor (GM-CSF). There are insufficient data available to allow the evaluation of the impact of prophylactic CSF on the incidence of toxic deaths in elderly patients with cancer and this is a crucial question for geriatric oncology practice. There is no evidence in elderly patients that the delivery of standard-dose chemotherapy on schedule improves efficacy measures. The data show that febrile neutropenic events are more likely to occur during the first and second cycles of chemotherapy, thus prophylactic measures should be considered early in the course of treatment. Furthermore, since systematic dose reduction can impact on outcome, primary prophylactic use of G-CSF for all elderly patients receiving curative myelotoxic chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like) is indicated and we suggest a risk-adapted strategy with primary prophylactic G-CSF administration in high-risk patients. Dose intensification, through dose interval reduction, facilitated by prophylactic G-CSF, improved survival in elderly patients with some specific diseases. There is a need for further well-designed studies to identify the elderly patients who will benefit most from prophylactic G-CSF. To achieve this, we strongly urge the design of and participation in further trials.

Aged↗
PubMed2001

Weekly docetaxel with either gemcitabine or vinorelbine as second-line treatment in patients with advanced nonsmall cell lung carcinoma: Phase II trials of the Minnie Pearl Cancer Research Network.

BACKGROUND: The current study was conducted to evaluate the feasibility, toxicity, and efficacy of weekly docetaxel when paired with either gemcitabine or vinorelbine as the second-line treatment of patients with advanced nonsmall cell lung carcinoma. METHODS: Patients with progressive nonsmall cell lung carcinoma after one previous chemotherapeutic regimen, an Eastern Cooperative Oncology Group performance status of 0-2, and measurable lesions were eligible for treatment in these Phase II trials. Patients who had not received gemcitabine previously were treated with docetaxel, 30 mg/m(2), and gemcitabine, 800 mg/m(2), both of which were administered intravenously (i.v.) on Days 1, 8, and 15 of a 28-day cycle. If the patients had received gemcitabine as part of first-line therapy, they were treated with docetaxel, 30 mg/m(2), and vinorelbine, 20 mg/m(2) i.v., on Days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after two courses of treatment, and responding patients continued treatment for six courses or until disease progression. RESULTS: Forty patients were treated with a combination of docetaxel and gemcitabine, and 23 patients received docetaxel and vinorelbine. The docetaxel/gemcitabine combination was reasonably well tolerated, with moderate myelosuppression and a few nonhematologic toxicities reported. The objective response rate was 10%, with a 1-year survival rate of 20%. The docetaxel/vinorelbine combination was found to be poorly tolerated, with Grade 3/4 leukopenia reported in 71% of patients and neutropenic fever reported in 70% of patients despite frequent dose reductions and omission of the Day 15 doses. Enrollment onto this regimen was stopped prematurely due to toxicity, and after no major responses were observed in the first 20 evaluable patients. CONCLUSIONS: The combination of weekly docetaxel/gemcitabine appears to be feasible and relatively well tolerated as second-line treatment in patients with advanced nonsmall cell lung carcinoma, whereas a weekly combination of docetaxel and vinorelbine did not appear to be tolerable at the doses and schedule used in the current study. Neither regimen showed a level of activity that suggested any advantage compared with the results obtained with single-agent docetaxel in this setting.

Adult↗
PubMed1983

Phase II evaluation of rubidazone (NSC-164011) in advanced carcinoma of the breast. A Southwest Oncology Group study.

The SWOG carried out a Phase II evaluation of rubidazone in patients with advanced breast cancer. Good risk patients were given rubidazone 150 mg/m2 IV every three weeks. Poor risk patients were given a 25% dose reduction at the start of treatment. Rubidazone dose was increased or decreased depending on toxicity. One patient went into complete remission, four had partial remission and nine had stable disease. Forty-two patients showed increased disease on treatment. No cardiotoxicity was seen, but other common toxicities noted included mostly mild to moderate myelosuppression, nausea, vomiting and alopecia. This study failed to indicate significant antitumor activity of rubidazone in patients with advanced breast carcinoma.

Aged↗
PubMed1996

Propafenone versus disopyramide for maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation: a randomized, double-blind study. PRODIS Study Group.

Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic atrial fibrillation (median arrhythmia duration, 5 months). After cardioversion, patients were randomly assigned to receive double-blind propafenone 300 mg tid (25 patients) or disopyramide 250 mg tid (31 patients). Downward dose adjustment was allowed in case of intolerable side effects. The endpoints were arrhythmia recurrence; and side effects not amenable to dose reduction. For patients randomized to propafenone (mean dose, 878 +/- 65 mg/day), 66% [95% confidence interval [(CI) 46-85%] and 55% (95% CI, 34-76%) remained in sinus rhythm at 3 and 6 months, respectively (Kaplan-Meier method). Similar figures were found with disopyramide (mean dose, 704 +/- 81 mg/day): 71% (95% CI, 54-87%) and 67% (95% CI, 50-84%) at 3 and 6 months, respectively (p = NS). In the patients with a relapse of atrial fibrillation, the ventricular rate while still using the prophylactic agents did not increase significantly compared with precardioversion. However, one patient on disopyramide had an excessively high relapse heart rate (170 vs. 100 beats/min). Side effects were more frequent on disopyramide. Side effects necessitating drug discontinuation occurred in 12 patients: 4 patients (16%) on propafenone and 8 (26%) on disopyramide. Severe adverse effects occurred in two patients, who developed heart failure while on disopyramide. There were no proarrhythmic events or deaths. Thus, propafenone and disopyramide are equally effective for maintaining sinus rhythm after cardioversion of atrial fibrillation. Propafenone is, however, better tolerated than disopyramide, which may cause heart failure.

Aged↗
PubMed2005

IMRT with compensators for head-and-neck cancers treatment technique, dosimetric accuracy, and practical experiences.

BACKGROUND AND PURPOSE: With three-dimensional conformal intensity-modulated radiotherapy (3D-c-IMRT) a heterogeneous dose distribution can be achieved in both planning treatment volume and in adjacent normal tissues and organs to be spared. 3D-c-IMRT demands for modified photon fluence profiles which can be accomplished with different techniques. This report deals with the commissioning of metal compensators and the first experiences in clinical use. Dosimetric accuracy, dose coverage and practical experience like treatment delivery time, monitor units and dose outside the treated volume are evaluated. PATIENTS AND METHODS: From January 2002 to April 2004, 24 patients with head-and-neck cancers were treated with 3D-c-IMRT using tin-wax compensators. The dose prescription included a simultaneously integrated boost (SIB). High-dose volume was irradiated with 60-70 Gy (median 66 Gy), low-dose volume with 48-54 Gy (median 52 Gy) administered by a standardized seven- portal coplanar beam arrangement. Dose at one parotid gland was aimed at 26 Gy. The compensators used consisted of tin granules embedded in wax; recalculation was performed with compensators made of the alloy MCP96 as well. RESULTS: In 21 of 24 patients 3D-c-IMRT with tin-wax compensators reduced the median dose to one parotid gland to < 30 Gy. Recalculation with compensators with higher density which allowed higher attenuation revealed better protection of the parotid gland. The treatment delivery time per fraction was between 6 and 12 min (plus time for patient positioning), approximately 300 MU per 2 Gy were applied. The dose outside the treated volume was increased with regard to open fields and comparable with a physical wedge of 15-30 degrees . Quality assurance and treatment of patient were fast and simple. It was shown, that calculated dose distribution corresponded to measured dose distribution with high accuracy. CONCLUSION: The described method offers facilities for a good dose coverage of irregular target volumes with different prescribed doses and a considerable dose reduction in adjacent organs at risk. The dose sparing of organs at risk can be further improved, if a compensator material with higher density is used.

Head and Neck Neoplasms↗
PubMed2006

Irofulven as first line therapy in recurrent or metastatic gastric cancer: a phase II multicenter study by the Cancer Therapeutics Research Group (CTRG).

BACKGROUND: The purpose of this study was to evaluate the tolerability and efficacy of irofulven, a DNA interacting acylfulvene analog, as first line therapy for patients with recurrent or metastatic gastric cancer. PATIENTS AND METHODS: Twenty-three patients with recurrent or metastatic gastric cancer received irofulven at a dose of 0.45 mg/kg administered intravenously over 30-min infusion (up to a maximum of 50 mg), on days 1 and 8, every 3 weeks. RESULTS: The median number of cycles delivered per patient was 2 (range 1-6). Two patients (9%) had >or= 1-week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, dose reductions were required in seven patients (30%); dose omitting occurred in five patients (22%). Grade 3/4 anemia and neutropenia occurred in 22 and 17% of patients, respectively. There was no grade 4 thrombocytopenia and no neutropenic fever was observed. Of the 20 evaluable patients, there were no responses observed, 3 patients had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55-9.39). CONCLUSIONS: Irofulven was tolerated at the dose of 0.45 mg/kg on days 1 and 8, every 3 weeks but showed no evidence of antitumor activity in patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed1991

A multicenter study of doxazosin in the treatment of patients with mild or moderate essential hypertension and concomitant intermittent claudication.

This study assessed the efficacy and safety of once-daily doxazosin in the treatment of patients (n = 19) with mild or moderate essential hypertension (sitting diastolic blood pressure [DBP] 95 to 114 mm Hg) and concomitant intermittent claudication (Doppler ankle/arm ratio of less than 0.80 and walking tolerance of less than 700 m on the treadmill). After 14 weeks of treatment with doxazosin, a significant (p less than 0.05) reduction in systolic blood pressure and DBP was observed. Mean blood pressures were reduced from 170/100 mm Hg at baseline to 161/93 mm Hg at the end of treatment. Minor changes in heart rate occurred, which with continued treatment were not statistically significant from baseline. In 12 of 16 (75.0%) efficacy-evaluable patients blood pressure was normalized (DBP to less than or equal to 90 mm Hg with an greater than or equal to 5 mm Hg reduction from baseline) with a mean daily dose of 7.6 mg/day. Doxazosin improved the hypertension severity category in 13 of 16 (81.3%) patients. The blood pressure ratios between both the thighs and arms and ankles and arms showed no statistically significant changes after treatment with doxazosin. Thigh blood flow at rest and the reactive hyperemia after 3 minutes of arterial occlusion did not change statistically. There was a tendency for pain-free distance to improve. Laboratory data were not significantly changed after treatment with doxazosin. Of the 19 patients studied, 5 reported mild or moderate side effects that were either tolerated or disappeared with continued treatment. No patient had therapy withdrawn and no patient required a dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed2000

Acute hematologic toxicity and practicability of dose-intensified BEACOPP chemotherapy for advanced stage Hodgkin's disease. German Hodgkin's Lymphoma Study Group (GHSG).

BACKGROUND: Evidence is recently accumulating that the novel BEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C), vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highly effective treatment for advanced stage Hodgkin's disease. Two dose variants of BEACOPP are currently tested in a phase III randomized multicenter trial of the GHSG. To enable more extensive testing of BEACOPP we characterized its practicability regarding schedule adherence, acute hematotoxicity and need for supportive treatment. PATIENTS AND METHODS: Data of 858 patients (6592 therapy cycles) from 184 participating institutions were evaluated. Planned total drug doses of the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480 mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1, the doses of E, A and C in the dose-intensified variant (arm 2) were escalated by factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dose reductions were specified in case of dose-limiting toxicities. Both variants are given in eight three-weekly courses. RESULTS: Median dose adherence (dose actually given relative to planned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalation of E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians), respectively, and 70% of patients maintained elevated dose levels throughout the entire treatment. Dose-limiting toxicities occurred in 25% of cycles in arm 2, most frequently due to leukocytopenia and thrombocytopenia. Time courses of leukocytes in arm 2 showed more severe but not more prolonged leukocytopenia compared with arm 1. WHO grades 3-4 infections were documented in 2.1% (arm 1) and 3.1% (arm 2) of all cycles. Erythrocytes were transfused in 61% (arm 1) and 28% (arm 2), platelets in < 1% (arm 1) and 6% (arm 2) of all cycles. CONCLUSIONS: Both BEACOPP schemes are practicable in a large multicenter setting. Despite increased hematotoxicity, moderate dose escalation is safe for the majority of the patients with G-CSF assistance and standard supportive treatment.

Adolescent↗
PubMed2001

High-Dose interferon-alpha2b plus ribavirin for retreatment of interferon-nonresponsive patients infected with genotype 1 hepatitis C virus.

Ten patients with interferon-nonresponsive chronic hepatitis C were treated with high-dose interferon-alpha2b (IFN-alpha2b; 20 MU/day for two days, then 3 MU/day for 24 weeks, followed by 3 MU three times weekly for 24 more weeks) plus ribavirin (1000-1200 mg/day). End-of-treatment virologic responses occurred in 50% of cases and sustained virologic responses in 37.5%. Hepatitis C virus RNA decreased significantly (2.15 logs; P < 0.0001) after the two 20-MU interferon doses but rebounded when the interferon dose was lowered to 3 MU/day. Thereafter, hepatitis C virus RNA showed a progressive, significant decrease, most notably at week 10 (3.3 logs; P = 0.001). Patients with a sustained response exhibited a more pronounced hepatitis C virus RNA decrease, especially from weeks 3 to 8 (P = 0.036). Two patients discontinued therapy because of adverse events, and one patient required a ribavirin dose reduction. Retreatment with an initial high-dose IFN-alpha2b plus ribavirin significantly reduces viral load in genotype 1-infected, interferon-nonresponsive patients.

Adult↗
PubMed1999

Transfer of radiographs.

Dental radiographs constitute 25% of all exposures made in the UK and therefore in terms of radiation protection the population risk is not insignificant. Paragraph 11 of The Core of Knowledge in the Schedule to the Protection of persons undergoing medical examination or treatment (POPUMET) regulations specifies the importance of using existing radiological information, whether films or reports, about a patient. The Guidance Notes recommends that in order to reduce unnecessary radiographic examinations, there should be ready availability of previous radiographs. Access to previous radiographs is also commended by the National Radiological Practice Board (NRPB) and the Royal College of Radiologists (PCR) in their report on Patient Dose Reduction in Diagnostic Radiology. In addition to dose limitation, patient care is improved.

Dental Records↗
PubMed2000

Retrospective appraisal of busulfan dose adjustment in children.

This report describes and critically appraises our experience with busulfan dose adjustment in children undergoing bone marrow transplant between April 1997 and March 1999. All children received an initial busulfan dose of 40 mg/m2 p.o. or by nasogastric tube. Whole blood samples were obtained 1, 1.5 and 6 h later and analyzed for busulfan content by gas chromatography with electron capture detection. The area under the whole blood busulfan concentration vs time curve (AUC) and an individualized dose which would achieve an AUC of 1300 microM/min were calculated. Mean and median busulfan doses were calculated using actual, ideal and effective body weight and stratified according to age. The relationship between the busulfan concentration at hour 6 and AUC was determined using linear regression. Thirty-nine courses of busulfan were evaluated in 38 patients. A change from the initial busulfan dose was required to achieve the target AUC in 34 courses (87%). Most children >1 to 5 years old required dose increments while most children >5 years old required dose reductions. Obesity did not significantly affect busulfan dose requirements. Busulfan concentrations at 6 h only weakly predicted the AUC achieved (r2 = 0.496; P = 0.001). Based on these findings, we recommend that the initial busulfan dose be assigned according to patient age and actual body weight. We also recommend that busulfan AUC be calculated for children using a four-sample (1, 1.5, 4 and 6 h) limited sampling technique.

Adolescent↗