کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2121942 1547116 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Defining dose-limiting toxicity for phase 1 trials of molecularly targeted agents: Results of a DLT-TARGETT international survey
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Defining dose-limiting toxicity for phase 1 trials of molecularly targeted agents: Results of a DLT-TARGETT international survey
چکیده انگلیسی

IntroductionIt is increasingly clear that definitions of dose-limiting toxicity (DLT) established for phase 1 trials of cytotoxic agents are not suitable for molecularly targeted agents because of specific toxicity profiles. An international survey collected expertise on the definition of DLT, as part of an initiative aimed at presenting new guidelines for phase 1 trials of targeted agents.MethodsA 15-question survey was sent to corresponding authors of phase 1 reports. Questions involved: duration of the DLT assessment period, incorporation of specific grade 1 (G1) or G2 toxicity and their minimum duration to qualify as DLT, exclusion of specific G3 and inclusion of dose modification/delay.ResultsAmong the 400 investigators contacted, 93 replied of whom 65 completed the questionnaires. A total of 87% opted for an extended DLT assessment period beyond cycle 1, with the proviso not to delay patient accrual. Reanalysis at the end of the study of all safety data was proposed in order to recommend the phase 2 dose. Most respondents (92%) suggested including dose modification in the definition of DLT when dose intensity was decreased to 70%. Whilst moderate toxicity was deemed relevant by 70%, the G1/2 toxicities selected to define DLT however varied.ConclusionThe majority of experts favoured a longer DLT assessment period as well as incorporation of specific G2 toxicities into the DLT definition. However, no clear consensus existed on a re-definition of DLT. Therefore analyses of a large international data warehouse were also used to develop guidelines presented in a companion paper.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 50, Issue 12, August 2014, Pages 2050–2056
نویسندگان
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