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Long-term Toxicity (long-term + toxicity)

Distribution by Scientific Domains

Medical Sciences	85%

Selected Abstracts

Long-term assessment of nevirapine-containing highly active antiretroviral therapy in antiretroviral-naive HIV-infected patients: 3-year follow-up of the VIRGO study

HIV MEDICINE, Issue 7 2006
V Reliquet
Objectives Data on the durability of antiretroviral regimens over a 3-year period have only rarely been reported. The aim of this study was to evaluate the long-term efficacy and safety of one or two daily doses of nevirapine (NVP), in combination with stavudine (d4T) and didanosine (ddI), in HIV-infected patients. Methods This study was a follow-up of the VIR (amune) Grand Ouest (VIRGO) study, a 12-month open-label trial to assess the safety and immunovirological activity of NVP-d4T-ddI combination therapy in antiretroviral-naive HIV-1-infected adults with baseline CD4 counts ,200 cells/,L and plasma viral loads ,5000 HIV-1 RNA copies/mL. Of the 100 patients included in the study, the 67 patients remaining on the initial triple therapy at the end of the study (1 year) were offered an extra 24 months of follow-up. Results Of the 60 patients who extended follow-up, 46 were still being treated with d4T-ddI-NVP at month 36; 91% (39/43) had a plasma viral load <500 copies/mL (data were missing for three patients). CD4 cell counts increased over 36 months. Safety and tolerance were good with no unexpected long-term toxicity. Conclusion After 3 years of treatment with NVP-d4T-ddI, nearly half of the patients were still receiving the initial antiretroviral therapy with a sustained and durable immunovirological benefit. Long-term toxicity was mainly related to the nucleoside reverse transcriptase inhibitor components of the regimen. [source]

Involved field radiotherapy for limited stage Hodgkin lymphoma: balancing treatment efficacy against long-term toxicities

HEMATOLOGICAL ONCOLOGY, Issue 3 2009
Jayant S. Goda
Abstract Limited stage Hodgkin lymphoma (HL) refers to patients with stage IA or IIA disease in the absence of any bulky mass or unfavourable prognostic factors. In this group, the long-term disease control with treatment can be expected in more than 90%, and management has now been directed to make strategies to reduce late morbidities related to therapy. With the advent of very effective chemotherapy, the role of radiation therapy has evolved from a first line single modality treatment, to an adjuvant therapy following brief cycles of chemotherapy. Optimal radiation volume and dose parameters have been refined in the combined modality setting. Furthermore, with the progress in diagnostic functional imaging and advances in radiotherapy, it is possible to accurately deliver low to moderate doses of radiation to defined regions resulting in durable control of disease. This review will evaluate the literature that shapes the current standard of care in limited stage Hodgkin lymphoma with special emphasis on the use of limited field radiotherapy. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Determinants of the optimal first-line therapy for follicular lymphoma: A decision analysis,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010
Rebecca L. Olin
Combination immunochemotherapy is the most common approach for initial therapy of patients with advanced-stage follicular lymphoma, but no consensus exists as to the optimal selection or sequence of available regimens. We undertook this decision analysis to systematically evaluate the parameters affecting the choice of early therapy in patients with this disease. We designed a Markov model incorporating the three most commonly utilized regimens (RCVP, RCHOP, and RFlu) in combinations of first- and second-line therapies, with the endpoint of number of quality-adjusted life years (QALYs) until disease progression. Data sources included Phase II and Phase III trials and literature estimates of long-term toxicities and health state utilities. Meta-analytic methods were used to derive the values and ranges of regimen-related parameters. Based on our model, the strategy associated with the greatest number of expected quality-adjusted life years was treatment with RCHOP in first-line therapy followed by treatment with RFlu in second-line therapy (9.00 QALYs). Strategies containing RCVP either in first- or second-line therapy resulted in the lowest number of QALYs (range 6.24,7.71). Sensitivity analysis used to determine the relative contribution of each model parameter identified PFS after first-line therapy and not short-term QOL as the most important factor in prolonging overall quality-adjusted life years. Our results suggest that regimens associated with a longer PFS provide a greater number of total QALYs, despite their short-term toxicities. For patients without contraindications to any of these regimens, use of a more active regimen may maximize overall quality of life. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source]

Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2008
Marta Medeot
Abstract Objective:, To evaluate the long-term activity and toxicity profile of rituximab in adult patients with idiopathic immune thrombocytopenic purpura (ITP). Patients and methods:, Twenty-six patients with active and symptomatic ITP relapsed or refractory received weekly infusions of rituximab 375 mg/m2 for 4 wk. Median time from diagnosis to rituximab was 34.5 months. The following parameters of efficacy and toxicity were considered: complete response (CR) and partial response (PR), relapse rate, relapse-free survival (RFS), therapy-free survival (TFS), short- and long-term toxicity. Results:, CR and PR were 14/26 (54%) and 4/26 (15%), respectively. Median time of observation was 56.5 months (range 39,77). Nine of the 18 responding patients relapsed after a median of 21 months (range 8,66); 9/26 patients (35%) maintained the response, with a median follow-up of 57 months (range 39,69), and 11/26 (42%) did not necessitate further therapy; estimated 5 yr RFS and TFS were 61% and 72%, respectively. Younger age and shorter interval from diagnosis to rituximab appeared indicators of better outcome. Rituximab administration was associated with two episodes of short-term toxicity, with one case of serum sickness syndrome; no infectious or other significant long-term complications were documented. Conclusion:, Rituximab therapy may achieve long-lasting remission in nearly one-third of patients with relapsed or refractory ITP, with a good safety profile. [source]

Long-term assessment of nevirapine-containing highly active antiretroviral therapy in antiretroviral-naive HIV-infected patients: 3-year follow-up of the VIRGO study

Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2010
PA Foley
Abstract Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short-term, their use is often limited by concerns over long-term toxicity, including end-organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF), receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNF,. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long-term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted. [source]

Determining a Maximum-Tolerated Schedule of a Cytotoxic Agent

BIOMETRICS, Issue 2 2005
Thomas M. Braun
Summary Most phase I clinical trials are designed to determine a maximum-tolerated dose (MTD) for one initial administration or treatment course of a cytotoxic experimental agent. Toxicity usually is defined as the indicator of whether one or more particular adverse events occur within a short time period from the start of therapy. However, physicians often administer an agent to the patient repeatedly and monitor long-term toxicity due to cumulative effects. We propose a new method for such settings. It is based on the time to toxicity rather than a binary outcome, and the goal is to determine a maximum-tolerated schedule (MTS) rather than a conventional MTD. The model and method account for a patient's entire sequence of administrations, with the overall hazard of toxicity modeled as the sum of a sequence of hazards, each associated with one administration. Data monitoring and decision making are done continuously throughout the trial. We illustrate the method with an allogeneic bone marrow transplantation (BMT) trial to determine how long a recombinant human growth factor can be administered as prophylaxis for acute graft-versus-host disease (aGVHD), and we present a simulation study in the context of this trial. [source]