کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5528152 1547961 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042)
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042)
چکیده انگلیسی


- Dacomitinib is a pan-HER inhibitor in development for advanced NSCLC.
- Impact of a 4-day dacomitinib dose interruption on plasma exposure and adverse events (AEs) was examined in a phase II study.
- Plasma pharmacokinetic parameters of dacomitinib before dose interruption were comparable to that from other dacomitinib studies.
- Average median plasma dacomitinib concentration during dose interruption was ∼50% of median plasma Cmax before dose interruption.
- The toxicity profile was consistent with that from other dacomitinib studies.

ObjectivesDacomitinib is a pan-HER inhibitor for advanced non-small-cell lung cancer (NSCLC). We explored the impact of a planned 4-day dacomitinib dose interruption on plasma exposure of dacomitinib and adverse events (AEs) of interest in Cohort III of the ARCHER 1042 study.Materials and methodsPatients, treatment-naïve for advanced NSCLC with EGFR activating mutations, received oral dacomitinib 45 mg QD (once daily). A planned dose interruption occurred in Cycle 1 from Days 11 through 14. The primary endpoint was the pharmacokinetic (PK) characteristics of dacomitinib in Cycle 1 Day 10 and during dose interruption. Secondary endpoints included safety and concomitant medications used to treat AEs of interest.ResultsCohort III enrolled 25 patients. Median plasma Cmax of dacomitinib in Cycle 1 Day 10 was 83.40 ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63 ng/mL. In the first 8 weeks of treatment 1) 80% of patients used concomitant medications for dermatologic AEs, 76% for diarrhea, and 44% for stomatitis, and 2) all patients experienced treatment-emergent AEs and 28% had all-causality Grade 3 AEs.ConclusionAt 45 mg QD dosing, PK parameters of plasma dacomitinib in Cycle 1 Day 10 were comparable to that obtained in Cycle 1 Day 14 from other dacomitinib studies. Average median plasma dacomitinib concentration during the 4-day dose interruption was approximately half of the median plasma Cmax of dacomitinib observed prior to dose interruption. The toxicity profile was consistent with that from other studies of dacomitinib.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Lung Cancer - Volume 106, April 2017, Pages 76-82
نویسندگان
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