Topic
Dose Modification
About: Dose Modification is a research topic. Over the lifetime, 193 publications have been published within this topic receiving 4149 citations.
Papers published on a yearly basis
Papers
TL;DR: Estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence are provided and it appears that the rate of dose delivery does not modify the low incidence for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease.
Abstract: This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.
1,461 citations
TL;DR: A certain proportion of Korean patients started therapy with a higher than targeted ribavirin dose, which resulted in more ribvirin dose modifications without definite additional benefit in achieving SVR, therefore, the ribaviral dosing regimen might need to be reassessed.
Abstract: BACKGROUND/AIMS The current recommendation of ribavirin dose for the treatment of chronic hepatitis C is based on study results of Western patients, and might not be optimal for Korean patients because of different body frames. METHODOLOGY A total of 163 treatment-naive genotype 1 chronic hepatitis C patients who received combination therapy with pegylated interferon a-2a and ribavirin were reviewed. RESULTS Under current ribavirin dosing, only 49% of patients started therapy with ribavirin dose of 13-15mg/kg (targeted dose), while 45% and 6% of patients started therapy with ribavirin dose =16mg/kg and <13mg/kg, respectively. Patients who started therapy with higher ribavirin dose experienced more ribavirin dose modification during treatment (55%, 31% and 11% for ribavirin dose of =16mg/kg, 13-15mg/kg and <13mg/kg, respectively, p=0.002). The sustained virological response (SVR) rate was 66%, 63% and 56% for ribavirin dose of =16mg/kg, 13-15mg/kg and <13mg/kg, respectively (p=0.775). CONCLUSIONS A certain proportion of Korean patients started therapy with a higher than targeted ribavirin dose, which resulted in more ribavirin dose modifications without definite additional benefit in achieving SVR. Therefore, the ribavirin dosing regimen might need to be reassessed.
608 citations
TL;DR: The quantitative clinical pharmacology approach provided evidence for regulatory decision-making on dose modification, obviating the need for an independent clinical study and establishing flat exposure–response relationships for efficacy and safety.
228 citations
Stanford University1, Harvard University2, Herlev Hospital3, University of Calgary4, University of Hamburg5, Ludwig Maximilian University of Munich6, European Institute of Oncology7, Katholieke Universiteit Leuven8, University College London9, University of British Columbia10, Free University of Berlin11, Poznan University of Medical Sciences12, Medical University of Vienna13, Copenhagen University Hospital14
TL;DR: The analysis presented suggests that patients with baseline body weight of <77 kg or baseline platelets of<150 000/µl may benefit from a starting dose of 200 mg/day, which was the most commonly administered dose in the ENGOT-OV16/NOVA trial.
164 citations
Journal Article•
TL;DR: No recommendation for dose modification based on abnormal cardiac findings in patients without clinical evidence of cardiotoxicity can be endorsed, including those of the Cardiology Committee of the Children's Cancer Study Group.
Abstract: Objective To review the basis for recommendations of the Cardiology Committee of the Children's Cancer Study Group, published in Pediatrics, for serial cardiac monitoring of cancer patients during anthracycline therapy and reduction of therapy should cardiac studies show abnormalities. Design Because the effects of overall morbidity and mortality should be considered when a recommendation is made to withhold potentially lifesaving chemotherapy based on abnormal cardiac findings of patients without clinical evidence of cardiac dysfunction, supporting studies referenced in the published recommendations were reviewed. Specifically, studies were evaluated to determine whether a reduction in anthracycline dose, as a result of abnormal cardiac findings by monitoring, reduced cardiac morbidity and related mortality compared with a prospectively followed control population without dose modification. In addition, the effects of cardiac monitoring and subsequent anthracycline dose modification on oncologic morbidity and mortality were reviewed in these studies. Finally, the contributions of the cardiac and oncologic effects of dose modification were examined to determine the effect of this change in therapy on overall morbidity and mortality. Results None of the studies cited in developing these recommendations prospectively determined, with controls, the effects of cardiac monitoring and anthracycline dose modification on cardiac, oncologic, or overall morbidity and mortality. Therefore, none of the studies cited in support of cardiac monitoring and subsequent dose reduction demonstrated the efficacy of such an approach. In the absence of such data, concerns are raised as to whether such a monitoring program with subsequent dose modification might do more harm than good. In addition, none of the methods of screening for anthracycline cardiotoxicity has been shown to be adequately predictive of early or late cardiac outcomes. Finally, adoption of these recommendations would inhibit the investigation of the efficacy of the proposed plan. Conclusion Given the absence of supportive data and the potential to do harm, no recommendation for dose modification based on abnormal cardiac findings in patients without clinical evidence of cardiotoxicity can be endorsed, including those of the Cardiology Committee of the Children's Cancer Study Group. When clinical evidence of cardiotoxicity is present, anthracycline dose modification is recommended. A prospective controlled study to determine the effects of dose modification based on cardiac test results is indicated.
133 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 4 |
| 2020 | 11 |
| 2019 | 15 |
| 2018 | 19 |
| 2017 | 9 |
| 2016 | 5 |