PMID- 28285698
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20191210
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Print)
IS  - 0169-5002 (Linking)
VI  - 106
DP  - 2017 Apr
TI  - Impact of a planned dose interruption of dacomitinib in the treatment of advanced 
      non-small-cell lung cancer (ARCHER 1042).
PG  - 76-82
LID - S0169-5002(17)30032-6 [pii]
LID - 10.1016/j.lungcan.2017.01.021 [doi]
AB  - OBJECTIVES: Dacomitinib 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 METHODS: Patients, 
      treatment-naive for advanced NSCLC with EGFR activating mutations, received oral 
      dacomitinib 45mg 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 1Day 10 and during dose interruption. 
      Secondary endpoints included safety and concomitant medications used to treat AEs 
      of interest. RESULTS: Cohort III enrolled 25 patients. Median plasma C(max) of 
      dacomitinib in Cycle 1 Day 10 was 83.40ng/mL. Average median plasma dacomitinib 
      concentration during the 4-day dose interruption was 42.63ng/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. 
      CONCLUSION: At 45mg 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 C(max) of dacomitinib 
      observed prior to dose interruption. The toxicity profile was consistent with 
      that from other studies of dacomitinib.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Kim, Dong-Wan
AU  - Kim DW
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, South 
      Korea. Electronic address: kimdw@snu.ac.kr.
FAU - Garon, Edward B
AU  - Garon EB
AD  - David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
FAU - Jatoi, Aminah
AU  - Jatoi A
AD  - Mayo Clinic, Rochester, MN, USA.
FAU - Keefe, Dorothy M
AU  - Keefe DM
AD  - University of Adelaide, Adelaide, Australia.
FAU - Lacouture, Mario E
AU  - Lacouture ME
AD  - Memorial Sloan Kettering Cancer Center, New York, NY, USA.
FAU - Sonis, Stephen
AU  - Sonis S
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Gernhardt, Diana
AU  - Gernhardt D
AD  - Pfizer Oncology, Groton, CT, USA.
FAU - Wang, Tao
AU  - Wang T
AD  - Pfizer Oncology, Groton, CT, USA.
FAU - Giri, Nagdeep
AU  - Giri N
AD  - Pfizer Oncology, La Jolla, CA, USA.
FAU - Doherty, Jim P
AU  - Doherty JP
AD  - Pfizer Oncology, New York, NY, USA.
FAU - Nadanaciva, Sashi
AU  - Nadanaciva S
AD  - Pfizer Oncology, Groton, CT, USA.
FAU - O'Connell, Joseph
AU  - O'Connell J
AD  - Pfizer Oncology, New York, NY, USA.
FAU - Sbar, Eric
AU  - Sbar E
AD  - Pfizer Oncology, Collegeville, PA, USA.
FAU - Cho, Byoung Chul
AU  - Cho BC
AD  - Yonsei University College of Medicine, Seoul, South Korea.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20170201
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Quinazolines)
RN  - 0 (Quinazolinones)
RN  - 5092U85G58 (dacomitinib)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - *Dose-Response Relationship, Drug
MH  - ErbB Receptors/antagonists & inhibitors/genetics
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Staging
MH  - Quinazolines/therapeutic use
MH  - Quinazolinones/administration & dosage/adverse effects/*blood/pharmacokinetics
MH  - Republic of Korea
MH  - Treatment Outcome
PMC - PMC5552055
MID - NIHMS887441
OTO - NOTNLM
OT  - Dacomitinib
OT  - Dose interruption
OT  - Non-small-cell lung cancer
OT  - Pharmacokinetic
OT  - Supportive care
COIS- Conflict of interest D-WK, SS, and BCC have no conflict of interest.
EDAT- 2017/03/14 06:00
MHDA- 2017/12/28 06:00
PMCR- 2017/08/10
CRDT- 2017/03/14 06:00
PHST- 2016/10/13 00:00 [received]
PHST- 2017/01/20 00:00 [revised]
PHST- 2017/01/29 00:00 [accepted]
PHST- 2017/03/14 06:00 [entrez]
PHST- 2017/03/14 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
PHST- 2017/08/10 00:00 [pmc-release]
AID - S0169-5002(17)30032-6 [pii]
AID - 10.1016/j.lungcan.2017.01.021 [doi]
PST - ppublish
SO  - Lung Cancer. 2017 Apr;106:76-82. doi: 10.1016/j.lungcan.2017.01.021. Epub 2017 
      Feb 1.