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Weekly Schedule (weekly + schedule)
Selected AbstractsFallacies of High-Speed HemodialysisHEMODIALYSIS INTERNATIONAL, Issue 2 2003Zbylut J. Twardowski Chronic hemodialysis sessions, as developed in Seattle in the 1960s, were long procedures with minimal intra- and interdialytic symptoms. Financial and logistical pressures related to the overwhelming number of patients requiring hemodialysis created an incentive to shorten dialysis time to four, three, and even two hours per session in a thrice weekly schedule. This method spread rapidly, particularly in the United States, after the National Cooperative Dialysis Study suggested that time of dialysis is of minor importance as long as urea clearance multiplied by dialysis time and scaled to total body water (Kt/Vurea) equals 0.95,1.0. This number was later increased to 1.3, but the assumption remained unchanged that hemodialysis time is of minimal importance as long as it is compensated by increased urea clearance. Patients accepted short dialysis as a godsend, believing that it would not be detrimental to their well-being and longevity. However, Kt/Vurea measures only removal of low molecular weight substances and does not consider removal of larger molecules. Besides, it does not correlate with the other important function of hemodialysis, namely ultrafiltration. Whereas patients with substantial residual renal function may tolerate short dialysis sessions, the patients with little or no urine output tolerate short dialyses poorly because the ultrafiltration rate at the same interdialytic weight gain is inversely proportional to dialysis time. Rapid ultrafiltration is associated with cramps, nausea, vomiting, headache, fatigue, hypotensive episodes during dialysis, and hangover after dialysis; patients remain fluid overloaded with subsequent poor blood pressure control, left ventricular hypertrophy, diastolic dysfunction, and high cardiovascular mortality. Short, high-efficiency dialysis requires high blood flow, which increases demands on blood access. The classic wrist arteriovenous fistula, the access with the best longevity and lowest complication rates, provides "insufficient" blood flow and is replaced with an arteriovenous graft fistula or an intravenous catheter. Moreover, to achieve high blood flows, large diameter intravenous catheters are used; these fit veins "too tightly," so predispose the patient to central-vein thrombosis. Longer hemodialysis sessions (5,8 hrs, thrice weekly), as practiced in some centers, are associated with lower complication rates and better outcomes. Frequent dialyses (four or more sessions per week) provide better clinical results, but are associated with increased cost. It is my strong belief that a wide acceptance of longer, gentler dialysis sessions, even in a thrice weekly schedule, would improve overall hemodialysis results and decrease access complications, hospitalizations, and mortality, particularly in anuric patients. [source] Adjuvant chemotherapy in colon cancer: what is the evidence?INTERNAL MEDICINE JOURNAL, Issue 3 2003A. Haydon Abstract Over the last 12 years, numerous randomized trials have addressed the role of adjuvant chemotherapy in resected colon cancer. Together, these studies give conclusive evidence of the benefit of adjuvant 5-fluorouracil combined with folinic acid in stage III (node positive) disease and this is now considered the standard of care. The chemotherapy appears to be equally effective whether it is given daily for 5 days per month or on a weekly schedule. The overall effect is a relative reduction in tumour recurrence of 25% or an absolute improvement in survival of 10%. However, doubt remains as to the role of adjuvant chemotherapy in stage II colon cancer. To date, most of the randomized trials have demonstrated a relative reduction in tumour recurrence but have not shown any significant impact on survival. It seems likely that this inability to demonstrate a survival benefit from adjuvant chemotherapy in stage II disease relates to the fact that the trials have been underpowered to do so. Nevertheless, the absolute survival advantage is only about 2% and clinicians need to weigh this against the costs and toxicities of the treatment when managing these patients. (Intern Med J 2003; 33: 119,124) [source] A phase I study of irinotecan administered on a weekly schedule in pediatric patientsPEDIATRIC BLOOD & CANCER, Issue 1 2006L. Bomgaars MD Abstract Background The objectives of this study were to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-tumor effect of irinotecan in pediatric patients with recurrent or refractory malignancies. Procedure Twenty-three patients between 1 and 21 years of age, with a solid tumor refractory to standard therapy or for which there was no standard therapy were enrolled. Irinotecan was administered over 90 min weekly 4×, every 6 weeks. The initial dose level was 125 mg/m2/day, with subsequent escalations to 160 and 200 mg/m2/day. A MTD was defined in heavily-pretreated and less-heavily-pretreated (,2 prior chemotherapy regimens, no prior bone marrow transplantation, and no central axis radiation) patients. Pharmacokinetic studies were also performed. Results Neutropenia and diarrhea were the DLTs in heavily pretreated patients; the MTD was 125 mg/m2/day. Neutropenia was the DLT in less-heavily pretreated; the MTD was 160 mg/m2/day. Five patients had stable disease for two to four cycles including one patient each with rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, and two patients with ependymoma. Irinotecan clearance was greater that that previously reported for children receiving high dose irinotecan. Conclusions The recommended phase II dose of irinotecan administered weekly 4×, every 6 weeks in children with solid tumors is 125 mg/m2/dose for heavily pretreated patients and 160 mg/m2/dose for less heavily pretreated patients. © 2005 Wiley-Liss, Inc. [source] Phase 2 study of weekly bortezomib in mantle cell and follicular lymphomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2009John Gerecitano Summary Twice-weekly bortezomib has proven activity in mantle cell (MCL) and indolent lymphomas. This study explored a weekly schedule of bortezomib in follicular lymphoma (FL) and MCL. Although weekly bortezomib was better tolerated, the overall response rate (ORR) was inferior (18% vs. 50%, P = 0·02) with no complete remissions (CR) (compared with 18% CR for the twice-weekly schedule). Progression-free survival (PFS) was not different. The weekly schedule of bortezomib was less toxic, but yielded fewer and lower quality responses than twice-weekly bortezomib. Given the similar PFS, the weekly schedule may still be appropriate for some patients. [source] Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3-weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer,CANCER, Issue 3 2008Suresh Ramalingam MD Abstract BACKGROUND. The purpose of this study was to compare the outcomes between elderly (aged ,70 years) patients treated with paclitaxel on a weekly basis and with carboplatin (every 4 weeks) versus the standard 3-weekly regimen of carboplatin and paclitaxel for first-line therapy of advanced nonsmall cell lung cancer. METHODS. Of the 444 patients enrolled, 136 (31%) were aged ,70 years. Seventy-two patients were randomized to the weekly schedule (paclitaxel, 100 mg/m2 weekly for 3 of 4 weeks; carboplatin, area under the curve [AUC] = 6 mg/mL·min on Day 1 every 4 weeks), and 64 patients were randomized to the standard schedule (paclitaxel, 225 mg/m2; carboplatin, AUC = 6 mg/mL·min on Day 1 every 21 days). Patients with stable disease or objective response after 4 cycles of therapy were eligible for maintenance therapy with weekly paclitaxel (70 mg/m2, 3 of 4 weeks). RESULTS. The response rate for elderly patients was 26% on the weekly regimen and 19% on the standard schedule. The median survival duration for the weekly and the standard schedules was 37 weeks and 31 weeks, respectively. The 1-year survival rates were similar at 31% and 33%. Grade 3 to 4 anemia was more common on the weekly schedule (16% vs 6%), whereas grade 3 neuropathy was less common (5.5% vs 9.5%). Nausea and emesis were also less frequent on the weekly schedule. CONCLUSIONS. Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile. Cancer 2008. © 2008 American Cancer Society. [source] Carboplatin hypersensitivity reaction in pediatric patients with low-grade gliomaCANCER, Issue 4 2008A Canadian Pediatric Brain Tumor Consortium experience Abstract BACKGROUND. Carboplatin-based regimens have demonstrated activity in pediatric patients with low-grade glioma (LGG). However, carboplatin hypersensitivity reaction (Cb HSR) represents a common and limiting factor for the continuation of therapy. METHODS. The objectives of this study were to describe the prevalence, characteristics, and management of Cb HSR and to detail their impact on outcome. The authors conducted a comprehensive, national, retrospective review of children who were diagnosed with LGG between 1985 and 2004 and received treatment with carboplatin. RESULTS. One hundred five patients from 10 Canadian centers were included. The median patient age at diagnosis was 3.5 years (range, 0.3,16.8 years), and 33 patients (31.4%) had neurofibromatosis type 1. Carboplatin was administered monthly in 46 children and weekly in 59 children. Forty-four patients (41.9%) developed Cb HSR after a median of 10.5 infusions (range, 3,39 infusions). Cb HSR occurred significantly earlier among children on the weekly schedule (4.4 months vs 9.1 months; P = .02). The first allergic reaction was grade I or II in 36 patients (82%). The cumulative incidence of Cb HSR increased with the number of infusions, and there was no evidence of a plateau. The only predictive factor was being a girl rather than a boy (P = .02). Thirty-four of 44 patients with Cb HSR were re-exposed to carboplatin, and 24 of 34 patients (70.5%) had recurrent Cb HSR. A desensitization approach did not provide any advantage compared with premedication alone for altering Cb HSR. The median number of additional Cb infusions delivered was 4 (range, 0.5,34 infusions). The effect of Cb HSR on the 5-year progression-free survival rate was not statistically significant (P = .1). CONCLUSIONS. Forty-two percent of children with LGG who received carboplatin regimens experienced Cb HSR. Most rechallenged children had recurrent Cb HSR despite Cb HSR-altering regimens. Cb HSR did not have an impact on progression-free survival. Cancer 2008. © 2007 American Cancer Society. [source] A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer,CANCER, Issue 5 2006Daniel T. Milton MD Abstract BACKGROUND. Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy. In the Phase I portion, patients were enrolled in 3-patient cohorts at erlotinib dose levels of 1200 mg, 1600 mg, and 2000 mg once weekly. The Phase II portion was designed to determine the major objective response rate of the dose identified in the Phase I portion of the trial. RESULTS. Twenty-seven patients were enrolled. No dose-limiting toxicity was observed. Grade 1 and 2 rash and diarrhea were the principle toxicities, and each occurred in 92% of patients. Among 21 patients who were treated at the Phase II dose of 2000 mg weekly, a single objective response was identified, yielding a response rate of 5% (95% confidence interval, 0.2,22%). For this cohort, the median survival was 9.5 months. The sole radiographic response occurred in a patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion. CONCLUSIONS. Erlotinib at a dose of 2000 mg administered weekly was tolerated well by these patients with advanced NSCLC. The 5% objective response rate did not reach the stated objective at the interim efficacy analysis, prompting the closure of the study. Cancer 2006. © 2006 American Cancer Society. [source] | ||||||||||