کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5528152 | 1547961 | 2017 | 7 صفحه PDF | دانلود رایگان |
- 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 â¼50% 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 45Â 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 1Â 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 1âDay 10 was 83.40Â ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63Â 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 45Â mg QD dosing, PK parameters of plasma dacomitinib in Cycle 1âDay 10 were comparable to that obtained in Cycle 1âDay 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.
Journal: Lung Cancer - Volume 106, April 2017, Pages 76-82