PMID- 23242861
OWN - NLM
STAT- MEDLINE
DCOM- 20130924
LR  - 20211021
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 31
IP  - 2
DP  - 2013 Apr
TI  - A Phase I, open-label, dose-escalation study of continuous once-daily oral 
      treatment with afatinib in patients with advanced solid tumors.
PG  - 409-16
LID - 10.1007/s10637-012-9904-9 [doi]
AB  - BACKGROUND: This trial evaluated the safety, tolerability and maximum tolerated 
      dose (MTD) of afatinib, a novel ErbB Family Blocker. METHODS: In this open-label, 
      dose-escalation Phase I study, afatinib was administered continuously, orally, 
      once-daily for 28 days to patients with advanced or metastatic solid tumors. Dose 
      escalation was performed in a 3 + 3 design, with a starting dose of 10 mg/day 
      (d); doses were doubled for each successive cohort until the MTD was defined. The 
      MTD cohort was expanded to a total of 19 patients. Incidence and severity of 
      adverse events (AEs), antitumor activity and pharmacokinetics were assessed. 
      RESULTS: Thirty patients received at least one dose of afatinib. Twenty-nine 
      patients were evaluable for response. Dose-limiting toxicities (DLTs) consisting 
      of Grade 3 diarrhea were observed in two out of three patients treated at 60 
      mg/d. The MTD was determined at 40 mg/d. The most frequent treatment-related AEs 
      were diarrhea and mucosal inflammation reported in 76.7% and 43.3% of patients 
      respectively. Five patients had stable disease with a median progression-free 
      survival of 111 days. No objective responses occurred. Pharmacokinetic data 
      showed no deviation from dose-proportionality and steady-state was reached on Day 
      8 at the latest. CONCLUSIONS: Afatinib was well tolerated with manageable side 
      effects when administered once-daily, continuously at a dose of 40 mg.
FAU - Gordon, Michael S
AU  - Gordon MS
AD  - Pinnacle Oncology Hematology, 9055 E Del Camino, Suite 100, Scottsdale, AZ 85258, 
      USA. mgordon@azpoh.com
FAU - Mendelson, David S
AU  - Mendelson DS
FAU - Gross, Mitchell
AU  - Gross M
FAU - Uttenreuther-Fischer, Martina
AU  - Uttenreuther-Fischer M
FAU - Ould-Kaci, Mahmoud
AU  - Ould-Kaci M
FAU - Zhao, Yihua
AU  - Zhao Y
FAU - Stopfer, Peter
AU  - Stopfer P
FAU - Agus, David B
AU  - Agus DB
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20121215
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Quinazolines)
RN  - 41UD74L59M (Afatinib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Afatinib
MH  - Aged
MH  - Aged, 80 and over
MH  - Cohort Studies
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Prognosis
MH  - Quinazolines/*pharmacokinetics/*therapeutic use
MH  - Tissue Distribution
PMC - PMC3589633
EDAT- 2012/12/18 06:00
MHDA- 2013/09/26 06:00
PMCR- 2012/12/15
CRDT- 2012/12/18 06:00
PHST- 2012/10/22 00:00 [received]
PHST- 2012/11/07 00:00 [accepted]
PHST- 2012/12/18 06:00 [entrez]
PHST- 2012/12/18 06:00 [pubmed]
PHST- 2013/09/26 06:00 [medline]
PHST- 2012/12/15 00:00 [pmc-release]
AID - 9904 [pii]
AID - 10.1007/s10637-012-9904-9 [doi]
PST - ppublish
SO  - Invest New Drugs. 2013 Apr;31(2):409-16. doi: 10.1007/s10637-012-9904-9. Epub 
      2012 Dec 15.