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At least 523 records · Page 29Linked to original sources
PubMed2005

Use of an automatic exposure control mechanism for dose optimization in multi-detector row CT examinations: clinical evaluation.

PURPOSE: To prospectively compare dose reduction and image quality achieved with an automatic exposure control system that is based on both angular (x-y axis) and z-axis tube current modulation with dose reduction and image quality achieved with an angular modulation system for multi-detector row computed tomography (CT). MATERIALS AND METHODS: The study protocol was approved by the institutional review board, and oral informed consent was obtained. In two groups of 200 patients, five anatomic regions (ie, the thorax, abdomen-pelvis, abdomen-liver, lumbar spine, and cervical spine) were examined with this modulation system and a six-section multi-detector row CT scanner. Data from these patients were compared with data from 200 patients who were examined with an angular modulation system. Dose reduction by means of reduction of the mean effective tube current in 600 examinations, image noise in 200 examinations performed with each modulation system, and subjective image quality scores in 100 examinations per-formed with each modulation system were compared with Wilcoxon signed rank tests. RESULTS: Mean dose reduction for the angular and z-axis tube current modulation system and for the angular modulation system was as follows: thorax, 20% and 14%, respectively; abdomen-liver, 38% and 18%, respectively; abdomen-pelvis, 32% and 26%, respectively; lumbar spine, 37% and 10%, respectively; and cervical spine, 68% and 16%, respectively. These differences were statistically significant (P < .05). There was no significant difference in image noise and mean image quality scores between modulation systems, with the exception of cervical spinal examinations (P < .001 for both), where the examinations with angular modulation resulted in better scores. There is good correlation between the mean effective tube current level and the body mass index of patients with the new modulation system. Correlation was as follows: thorax, 0.77; abdomen-pelvis, 0.83; abdomen-liver, 0.84; lumbar spine, 0.8; and cervical spine, 0.6. This correlation was not observed with the angular modulation system. CONCLUSION: An automatic exposure control mechanism that is based on real-time anatomy-dependent tube current modulation delivers good image quality with a significantly reduced radiation dose.

Adolescent↗
PubMed2005

Optimization of conformal avoidance: a comparative study of prone vs. supine interstitial high-dose-rate breast brachytherapy.

PURPOSE: Several recent studies indicate high-dose-rate (HDR) breast brachytherapy as an alternative to standard external beam radiation therapy for partial breast irradiation with high dose conformality to the target. However, this article presents an exploration of the possibility of achieving higher conformal avoidance of sensitive structures through detailed and comparative 3D CT-based anatomical dose distribution of a patient in supine and prone positions. METHODS AND MATERIALS: A patient treated with accelerated partial breast HDR breast brachytherapy in the supine position was selected for two CT-based analyses, one in the supine and one in the prone position. The optimized plan (Nucletron HDR planning station) for each position was achieved using graphical optimization with local adjustment of isodose lines to cover the planned target volume (PTV, lumpectomy with 2 cm margin) with 100% of the prescribed dose (34 Gy in 10 fractions) while minimizing the hot spots. Cumulative dose-volume histograms (DVH) were analyzed for the PTV, lung, skin, pectoral muscle, and chest wall. RESULTS: The PTV received 100% of prescribed dose in both the prone and supine positions. A significant (>40%) dose reduction was achieved in the lung in the prone treatment position. Similar dose reductions were also achieved for prone pectoral muscle, chest wall, and breast skin, irradiating less volume with high doses. Pectoral muscle, lumpectomy, and the breast skin showed prominent differences in shape and displacement in the prone compared with the supine position. CONCLUSION: CT-based treatment planning allowed calculations of volumetric dose distribution to the target and all sensitive structures with proper visualization and volumetric delineation of organs of interest. The treatment plan shows significant dose reduction may be possible in various sensitive structures if the patient is treated with HDR brachytherapy in the prone position.

Breast Neoplasms↗
PubMed1990

Phase II trial of intermittent high-dose recombinant interferon alfa-2a in mycosis fungoides and the Sézary syndrome.

We previously demonstrated that recombinant interferon alfa-2a (IFN-alfa) in a dose of 50 X 10(6) U million units (MU)/m2 intramuscularly (IM) three times per week has efficacy against mycosis fungoides (MF) and the Sézary syndrome (SS). However, this regimen given to patients with refractory disease was uniformly complicated by toxicities requiring major dose reductions. The present study was designed to determine if intermittent high-dose IFN-alfa would preserve efficacy and decrease toxicity in a similar patient population. Twenty-four patients with advanced disease refractory to one or more standard therapies received IFN-alfa, 10 MU/m2 IM on day 1 followed by 50 MU/m2 IM on days 2 to 5 every 3 weeks; after the first four cycles, stable and partially responding patients underwent dose escalation to twice the starting dose. One complete (CR) and six partial responses (PRs) were observed (response rate, 29%; 95% confidence interval, 13% to 51%) lasting 4 to 19 months (median, 8 months). No improvement in objective response was seen in the eight patients who received dose escalation. Dose reductions were necessary in eight of 22 patients receiving one or more cycles of therapy. Weighted mean dose rate intensity for patients on this study over the first four cycles of treatment was 65.5 MU/m2/wk compared with 73.2 MU/m2/wk over the first 12 weeks of treatment in patients from the previous study, in which all 19 patients receiving more than 1 week of treatment required dose reduction. IFN-alfa is effective against previously treated MF and the SS and is better tolerated on this intermittent schedule.

Combined Modality Therapy↗
PubMed1976

Volume and time factors in interstitial gamma-ray therapy.

The two suppositions which have dictated time-dose and volume relationships in interstitial gamma ray implantation have been examined in the light of recent publications. The first of these assumptions, that total dose reduction is required when the dose rate exceeds 6,000-7,000 rads in seven days, does not appear to be substantiated by clinical experiences. It appears that total dose is the critical treatment parameter and that dose rate may be increased by a factor of two or three without requiring alteration of the total dose. Although the second classical assumption, "volume increase requires dose decrease," has been shown throughout radiation therapy experience to be generally correct, it should not be applied rigidly to interstitial gamma-ray therapy. In fact, recent experiences seem to indicate that compensation with respect to volume is not an absolute necessity. Larger lesions require, if anything, higher doses than small ones. To obtain a high percentage of controlled, lesions there must be no dose reduction, regardless of increased volume treated.

Animals↗
PubMed1998

Neoral conversion from Sandimmune in maintenance renal transplant patients: an individualized approach.

When converting maintenance renal allograft recipients from Sandimmune (cyclosporin A [CsA]) to Neoral (CsA-microemulsion [CsA-ME]), a dose conversion ratio of 1:1 may not be optimal, in part because of the variability in absorption of the CsA formulation of cyclosporine. After conversion using a 1:1 dose ratio, an individualized approach to the management of dosing was applied. In this article, close monitoring, which began at the time of conversion, and rapid response to potentially meaningful changes in cyclosporine trough levels early in the postconversion course were used to maintain patients' cyclosporine troughs at preconversion levels. The results of cyclosporine dose changes after converting stable, maintenance renal transplant patients from CsA (once daily and twice daily) to CsA-ME (twice daily) during 52 wk of follow-up are reported. Most patients (87.2%) required CsA-ME dose reduction to maintain preconversion trough levels, and 64% of the patients attained their CsA-ME maintenance dose by study week 4. Logistic regression analysis identified one significant predictor concerning the week 52 CsA-ME dose: patients converted from CsA doses > or = 4.0 mg/kg per d were more likely to require dose reduction (P < 0.0001). Although firm guidelines for dose modification after conversion from CsA to CsA-ME cannot be provided because of the individual nature of cyclosporine absorption, an individualized approach to patient management is recommended. Patients with higher CsA doses before conversion are particularly likely to require dose reduction early in the postconversion course. With CsA-ME, good absorbers of cyclosporine remain good absorbers, or become better absorbers, whereas poor absorbers become good absorbers.

Adult↗
PubMed1994

Safety of esmolol in patients with acute myocardial infarction treated with thrombolytic therapy who had relative contraindications to beta-blocker therapy.

OBJECTIVE: This study was conducted to evaluate the safety of esmolol in 114 patients treated with thrombolytic therapy for acute myocardial infarction who also had relative contraindications to beta-blockade, and the predictive value of patient tolerance to esmolol and subsequent patient tolerance of oral beta-blocker therapy. PATIENTS: One hundred and fourteen patients with myocardial infarction documented by enzyme concentrations and electrocardiographic changes who also had relative contraindications to beta-blockade. METHODS: Esmolol was initiated during acute myocardial infarction for myocardial ischemia (n = 88), hypertension (n = 13), or supraventricular tachycardia (n = 13). Relative contraindications to beta-blocker therapy included either active signs/symptoms of left ventricular dysfunction or a history of congestive heart failure (n = 40), a history of chronic obstructive pulmonary disease or asthma (n = 31), bradycardia (HR < 60 beats/min; n = 18), peripheral vascular disease (n = 15), or hypotension (systolic BP < 100 mm Hg; n = 14). RESULTS: During initial esmolol dose titration, 69 patients tolerated 300 micrograms/kg/min, 12 patients tolerated 200 micrograms/kg/min, 17 patients tolerated 100 micrograms/kg/min, and 16 patients tolerated 50 micrograms/kg/min. Twenty-eight patients (25 percent) developed dose-limiting adverse effects during esmolol maintenance infusions. Sixteen patients required esmolol dose reduction and 12 required esmolol discontinuation. Adverse effects reversed within 30-45 minutes following dose reduction or discontinuation. The 86 patients who tolerated esmolol infusions without dose reduction or drug discontinuation were subsequently treated with oral beta-blockers. Eleven of these patients (13 percent) developed adverse effects requiring oral beta-blocker discontinuation. Nine of these patients had tolerated only 50 micrograms/kg/min of esmolol, and the other 2 patients had tolerated only 100 micrograms/kg/min. CONCLUSIONS: Esmolol can be used safely in most patients treated with thrombolytic therapy for acute myocardial infarction who have relative contraindications to beta-blockers. Tolerance to higher maintenance doses of esmolol is a good predictor of subsequent outcome with oral beta-blocker therapy.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations.

Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (MLT), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer. The study included 30 metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5-fluorouracil, who were randomized to be treated with CPT-11 alone or CPT-11 plus MLT. According to a weekly low-dose schedule, CPT-11 was given i.v. at 125 mg/m2/week for 9 consecutive weeks. MLT was administered orally at 20 mg/day during the dark period of the day. No complete response was observed. A partial response (PR) was achieved in 2 out of 16 patients treated with CPT-11 alone and in 5 out of 14 patients concomitantly treated with MLT. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with CPT-11 alone and in 7 out of 14 patients treated with CPT-11 plus MLT. Therefore, the percent of disease-control achieved in patients concomitantly treated with MLT was significantly higher than that observed in those treated with chemotherapy alone (12 out of 14 vs 7 out of 16, p < 0.05). The only important toxicity was diarrhoea grade 3-4, which occurred in 6 out of 16 patients treated with CPT-11 alone and in 4 out of 14 patients treated with CPT-11 plus MLT, which required a 50% dose reduction. However, taken together, patients treated with CPT-11 at 50% of the planned dose showed a percent of disease control comparable to that achieved in patients who had no dose reduction (6 out of 10 vs 13 out of 20). This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT, according to the results previously reported for other chemotherapeutic agents. Moreover, since the dose reduction of CPT-11 does not influence its efficacy, the dose of CPT-11 for successive studies might be not greater than 70 mg/m2.

Adjuvants, Immunologic↗
PubMed1994

Dose-reducing effect of Lipowitz metal-embedded spacers in interstitial brachytherapy for carcinoma of the mobile tongue.

Dose-reducing effects of spacers with and without a Lipowitz metal plate for the purpose of decreasing osteoradionecrosis after interstitial brachytherapy for tongue cancers were examined experimentally and clinically. The thicker the sample or spacer and the thicker the metal plate, the greater was the dose reduction achieved. A more marked dose reduction was achieved with iridium than with radium because of lower gamma ray energy of iridium. Iridium has been used widely as a radioactive source for interstitial brachytherapy. It was concluded therefore that a metal plate should be used as a shield into the spacer in interstitial brachytherapy both to reduce the radiation dose to surrounding normal tissues and to help prevent osteoradionecrosis.

Alloys↗
PubMed1997

A phase II study of doxorubicin/paclitaxel plus G-CSF for metastatic breast cancer.

This phase II trial was conducted to evaluate the percentage of objective responses and the toxicity profile of combination doxorubicin (Adriamycin) and paclitaxel (Taxol) with granulocyte colony-stimulating factor as first-line therapy for patients with metastatic breast cancer (MBC) not previously exposed to anthracycline-containing regimens. Patients with measurable, visceral-dominant MBC and a performance status of 0 to 2 were included in the study. Doxorubicin 60 mg/m2 was administered as a short intravenous infusion, followed by paclitaxel 250 mg/m2 as a 3-hour intravenous infusion on day 1. Granulocyte colony-stimulating factor 5 micrograms/kg/d was given prophylactically as a subcutaneous injection from day 2 until granulocyte recovery to > or = 1,500/mm3. Treatment was repeated every 21 days for a maximum of six courses. Dose reductions (to doxorubicin 50 mg/m2 and paclitaxel 175 mg/m2) and/or treatment delay were applied in case of severe toxicity. All 25 women who entered were evaluable for response and toxicity. The main grade 3/4 toxicities observed were leukopenia, thrombocytopenia, and mucositis. Alopecia occurred in all patients. No clinically relevant cardiovascular toxicity was observed. Severe myelosuppression and/or mucositis necessitated dose reductions at courses 2 or 3 in all but one patient. The complete response rate was 28%, and the partial response rate was 52% for an overall objective response rate of 80%. Median progression-free survival for complete responders was 11 months (range, 3 to 24 months), while the progression-free survival was 7+ months (range 2 to 14+ months) for partial responders and 5 months (range, 3 to 9 months) for nonresponders. This combination produces a high objective response rate in women with MBC, but dose reductions were necessary in almost all cases. Toxicity was manageable after dose reduction, allowing patients to be re-treated for two to six courses without life-threatening toxicity or toxic deaths. Unfortunately, the duration of response was limited even among complete responders. Further trials of this combination in patients with MBC should explore improvements in this study regimen.

Adult↗
PubMed2005

A phase II trial of weekly paclitaxel and every 3 weeks of carboplatin in potentially platinum-sensitive ovarian and peritoneal carcinoma.

OBJECTIVE: Paclitaxel administered weekly in equal cumulative doses is associated with less hematologic and non-hematologic toxicity than an every 3-week administration. We studied weekly paclitaxel and 3-week carboplatin in potentially platinum-sensitive recurrent ovarian and peritoneal carcinoma. METHODS: Paclitaxel at a dose of 80 mg/m(2) over 1 h in combination with carboplatin at an AUC of 5 was administered on day 1. Subsequent paclitaxel doses, modified based on the day of treatment ANC, were administered on days 8 and 15. Paclitaxel dose reductions to 75% of prior dose were performed for chemotherapy delays or toxicity. RESULTS: Twenty-eight patients were studied. The median age was 59 (range 42-80). The median platinum-free interval was 12 months (range 7-129 months). A median of six courses (range 1-13) was administered. Paclitaxel dose reductions to 60 mg/m(2) were required in 85% of the patients. Grades 3 and 4 thrombocytopenia were seen in 5 and 0 patients, respectively. Grades 3 and 4 neutropenia were seen in 14 and 1 patients, respectively. One patient was hospitalized for neutropenic fever. Twenty of 26 (77%) evaluable patients have responded with 15 patients (58%) achieving a complete response. CONCLUSIONS: Weekly paclitaxel at a dose of 60 mg/m(2) in combination with carboplatin at an AUC of 5 is well tolerated and active in potentially platinum-sensitive recurrent ovarian and peritoneal carcinoma.

Adult↗
PubMed2002

Topotecan in combination with carboplatin: phase I trial evaluation of two treatment schedules.

BACKGROUND: Topotecan and cisplatin combinations have shown schedule-dependent toxicity, which may in part be due to cisplatin nephrotoxicity. As carboplatin is less nephrotoxic and increasingly replacing cisplatin in clinical practice, the aim of this study was to define the optimal sequence and dose for topotecan in combination with carboplatin. PATIENTS AND METHODS: Two parallel phase I trials, with pharmacokinetic studies, were conducted administering carboplatin on day 1 with topotecan on days 1-5 (schedule A) or days 8-12 (schedule B). repeated every 3 weeks. RESULTS: Twenty-one patients were treated over two dose levels, carboplatin AUC 4 [glomerular filtration rate (GFR) calculated from 51Cr-EDTA clearance] with topotecan 0.5 or 0.75 mg/m2. At the first dose level, six patients were evaluable for each schedule. With schedule A, from 34 cycles, there were two dose reductions and 10 treatment delays due to myelosuppression. With schedule B from 25 cycles, there was one reduction and 10 delays. At dose level 2, both patients in schedule A had dose-limiting neutropenia. In contrast, there was no dose-limiting toxicity with schedule B in six patients, although the majority of cycles were delayed. CONCLUSION: The combination of topotecan and carboplatin using these 3-weekly schedules lead to significant myelotoxicity with attendant dose reductions and delays; the optimal scheduling of these agents remains to be defined.

Adult↗
PubMed2006

Chronotherapeutic dose schedule of phenytoin and carbamazepine in epileptic patients.

The objective of this study was to compare the efficacy and safety of a chronotherapeutic dosing schedule of phenytoin and carbamazepine versus a conventional dosing schedule for the treatment of tonic-clonic epileptic patients. Of 148 epileptic subjects found to have subtherapeutic trough drug levels (subtherapeutic group, STG), 103 subjects who completed the study were randomized to either STG I (n=51) for treatment by the conventional dosing schedule (tablet phenytoin 100-400 mg/day OD or BD, tablet carbamazepine 200-800 mg BD, or both, equally divided doses with no fixed time of drug intake), with a dose increment but no change in usual time of drug administration allowed; or to STG II (n=52), with no dose increment permitted but a shift in all or most (two-thirds or three-fourths) of the daily dose of one or both medications to 20:00 h. The 62 patients who experienced drug toxicity reactions (toxicity group, TG) and who had serum drug levels in the toxic range were assigned to TG I for dose reduction or TG II for dose reduction and drug administration at 20:00 h. Those 16 subjects in STG I and 47 subjects in STG II who initially evidenced subtherapeutic trough drug concentrations exhibited therapeutic drug levels by the end of four weeks of treatment (p<0.01). A significantly greater number of TG II, as compared to TG I, subjects who experienced toxic reactions showed improved drug tolerance. There were no poor responders and more good responders (control of epilepsy for one year) in STG II compared to STG I subjects. The findings of this study indicate that a chronotherapeutic dosing schedule of phenytoin and carbamazepine involving the administration of most or all the daily dose of medication(s) at 20:00 h can improve the response of diurnally active epileptic patients not responding to standard doses, achieve therapeutic drug levels, and reduce toxic manifestations in subjects having drug concentrations beyond the therapeutic range.

Adolescent↗
PubMed1998

Risks associated with conversion of stable patients after liver transplantation to the microemulsion formulation of cyclosporine.

BACKGROUND: Neoral is a microemulsion formulation of cyclosporine that has a better pharmacokinetic profile than the standard formulation (Sandimmune). To prove the safety of converting stable liver transplant patients from Sandimmune to Neoral, we conducted a prospective trial involving 54 patients. METHOD: The average time from transplantation to conversion was 48.5+/-21.6 months. Thirty of 54 patients (55%) required a dose reduction during the study for various reasons. Five of 30 patients had the first dose reduction because of increased levels of cyclosporine. Seven patients required more than one dose reduction. RESULTS: Sixteen patients suffered serious adverse events. Six patients had a biopsy-proven rejection. Four of 6 patients had trough cyclosporine levels within 20% of baseline value immediately before developing rejection. CONCLUSION: Converting patients from the standard formulation to the microemulsion formulation of cyclosporine seems to expose stable patients to unnecessary risks.

Adolescent↗
PubMed2006

Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV treatment in HIV-infected persons.

Anaemia during peginterferon (PEG-IFN) and ribavirin (RBV) therapy is common in human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients despite the use of lower doses of RBV than are recommended for HIV-seronegative persons. In addition, concurrent zidovudine (ZDV) may exacerbate the anaemia caused by PEG-IFN and RBV. We retrospectively analysed the incidence of anaemia, RBV dose reduction and epoetin-alpha (EPO) use among coinfected patients treated with PEG-IFN and weight-based RBV (800-1400 mg/day) who enrolled in two clinical trials and had haemoglobin (Hb) levels assessed at baseline and after 4 and/or 12 weeks of HCV treatment. Overall, 217 patients were included; pre-treatment Hb levels (mean 14.7 g/dL) were similar in all patients, including ZDV users (29% of patients). After 4 weeks of therapy, the mean Hb decline was greater among ZDV recipients (3.13 g/dL) compared with those on other anti-retroviral treatment (ART) (2.13 g/dL) or on no ART (1.47 g/dL) (P < 0.0001). RBV dose reduction and EPO use were more common in patients taking ZDV compared with those not taking ZDV (P < 0.0001). RBV dose was not associated with Hb reduction, RBV dose reduction or EPO use. Virologic response after 12 weeks of therapy and the treatment discontinuation rate did not differ by ZDV use. The use of ZDV but not weight-based RBV dosing was associated with an increased risk of anaemia, RBV dose reduction or EPO use in coinfected patients treated with PEG-IFN/RBV. However, ZDV use was not associated with higher rates of treatment discontinuation or lower early virologic response rates. HIV and hepatitis C care providers should be cognizant of these data.

Adult↗
PubMed1987

Recombinant interferon A (IFL-rA) therapy of small cell and squamous cell carcinoma of the lung. A phase II study.

Recombinant interferon A (50 x 10(6) U/m2 three times weekly) was given to 17 patients with SCCL and 13 patients with SQL. The minimal scheduled duration of therapy was 12 weeks. Fifteen and 11 patients, respectively, were evaluable for response. All 15 patients with SCCL showed progressive disease after a period of 2.5 weeks (median; range 1-13). One patient with SQL obtained a partial remission lasting 14 months and six patients showed no change for 14-20 weeks, while the remaining patients showed progression during the initial 12 week period. Toxicity was shown to be significant and only one patient completed therapy without dose reduction. The major cause of dose reduction was fatigue and anorexia (18 patients). Fourteen patients experienced a median weight loss of 6%. Haematological and hepatological toxicity was found in six and 19 patients, respectively. In most cases parameters of marrow and liver function were reversible in spite of continuing interferon treatment.

Adult↗
PubMed1998

Bolus/infusional 5-fluorouracil and folinic acid. A report on two prospective, consecutive phase II studies with 5-fluorouracil dose escalation.

We have used a relatively new trial methodology, the group sequential design, to prospectively evaluate two dose levels of bolus/infusional 5-fluorouracil (5-FU) and folinic acid in 192 consecutive-patients with advanced colorectal carcinoma. On day 1, all patients received 200 mg m(-2) of folinic acid infusion over 2 h. Cohort A (n = 102 patients) received 500 mg m(-2) 5-FU by i.v. 15-min infusion followed by an infusion of 500 mg m(-2) 5-FU over 22 h. Treatment was repeated on day 2 and further cycles given 2-weekly. After sequential analysis excluded a response rate of over 40%, cohort B (n = 90 patients) received an increased dose of 600 mg m(-2) 5-FU bolus and infusion. Patients had received no prior 5-FU therapy and the two cohorts had similar demographic features. In 179 evaluable patients, the overall response rate was 18% (95% CI 12-24%) with CR of 6% and PR of 12%, with no difference between the two cohorts. Overall median survival was 34 weeks (95% CI 30-39) with no significant difference between cohorts (median survival 32 and 37 weeks in cohort A and B respectively; P = 0.27). On multivariate analysis, poor performance status, elevated initial WBC and alkaline phosphatase and low serum albumin were associated with reduced survival (P < 0.05), and initial raised WBC showed an association with reduced likelihood of response (P = 0.002). Overall toxicity was low with CTC grade 3 mucositis, diarrhoea, nausea or vomiting in < or = 6% of patients and no treatment-related deaths. Significant (grade 3 or above) leucopenia was more common in cohort B than in cohort A (9% and 1% respectively); there were more dose reductions, and the median administered dose intensity was lower in cohort B than in cohort A (89% and 97% respectively; P = 0.006). In this group of relatively unselected patients, we have confirmed a relatively low objective response rate and median survival of 7.8 months with this regimen. There was no significant difference in outcome between the two dose levels but the higher dose of 5-FU was associated with more dose reductions and greater toxicity.

Adult↗
PubMed2004

A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year.

BACKGROUND: In an attempt to reduce chronic calcineurin inhibitor induced allograft nephropathy in first cadaver and human leukocyte antigen non-identical living-donor renal transplantation, sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive therapy, with planned dose reductions of tacrolimus (Tacro) over the first year postoperatively. Adjunctive Siro therapy with a similar dose reduction algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and Siro, group C) is described in our companion report in this issue of Transplantation. The present report documents function, patient and graft survival, protocol compliance, and adverse events. RESULTS: As mentioned (in companion report), group demographics were similar. The present study shows no significant differences in 1-year patient and graft survival but does show a trend that points to more difficulties in group C by way of a rising slope of serum creatinine concentration (P=0.02) and decreasing creatinine clearance (P=0.04). There were more patients who discontinued the protocol plan in group C. Thus far, no posttransplant lymphomas have appeared, and infectious complications have not differed among the groups. However, a greater percentage of patients in group C were placed on antihyperlipidemia therapy, with an (unexpected) trend toward a higher incidence of posttransplant diabetes mellitus in this group. Group A required fewer, and group B the fewest, antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This 1-year interim analysis of a long-term, prospective, randomized renal-transplant study indicates that decreasing maintenance dosage of Tacro with adjunctive Siro or MMF appears to point to improved long-term function, with reasonably few adverse events.

Creatinine↗
PubMed2006

Dosimetric analysis of a shielded applicator for nasopharyngeal carcinoma intracavitary brachytherapy: Monte Carlo calculation.

In nasopharyngeal cancer (NPC) intracavitary brachytherapy, an anatomical dose reference point (in line with that for gynecology work), e.g., at the sphenoid floor, is more precise than the empirical point of 1 cm from the source. However, such increases of the single-source-plan treatment distances may deliver excessive doses inferiorly, to the soft palate. As shielding may help, its efficacy was studied by Monte Carlo simulations in water for 20 and 30 mm diameter spherical NP applicators (representing extremes of sizes for the small NP cavity), with/without lead shielding inferiorly, using a single linear Ir-192, 2 mm steps, equal dwell times for 5 (5DP) and 9 dwell positions (9DP). Dose reductions of the selected points of interest ranged from 1.2% to 40.5% for the 20 mm shielded applicator and a range of 2.9% to 17.9%, for the 30 mm shielded applicator. Dose volume histograms of the "region of interest" (ROI)-a cuboid of 4 x 4 x 0.5 cm3 at the most inferior aspect of the applicator, also differed significantly. The highest doses of the 50% (D50) and 20% (D20) volumes of ROI (for 5DP and 9DP plans) were reduced by 11.9% to 17.9% for the 20 mm applicator and a range of 9.0% to 11.5% for the 30 mm shielded applicator. Doses in unshielded directions were insignificantly changed, for example, with a 20 mm applicator simulated in a 5DP plan, the dose distribution close to the source in the unshielded direction has less than 4% difference at the 50% isodose relative to the dose prescription point. For the 30 mm shielded applicator, despite smaller dose reduction percentages, a more pronounced effective dose reduction was obtained than nominal values when considering radiobiological equivalent doses. Our system was demonstrated to be ready for clinical assessment.

Brachytherapy↗