PMID- 29748012
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20221207
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 120
DP  - 2018 Jun
TI  - A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line 
      therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3).
PG  - 27-33
LID - S0169-5002(18)30297-6 [pii]
LID - 10.1016/j.lungcan.2018.03.007 [doi]
AB  - BACKGROUND: There are limited treatment options for squamous non-small cell lung 
      cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) 
      of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as 
      first-line treatment for advanced sqNSCLC patients, were evaluated. MATERIALS AND 
      METHODS: A phase I, dose-escalation study administering drugs in a 21-day cycle: 
      cisplatin (75 mg/m(2), Day 1), gemcitabine (1250 mg/m(2), Days 1 and 8) and 
      nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy 
      until disease progression or adverse events (AEs). Two nintedanib doses were 
      tested, 150 mg twice daily (bid) and 200 mg bid, to determine maximum tolerated 
      dose (MTD) based on occurrence of dose-limiting toxicities (DLTs) during Cycle 1. 
      DLTs were primarily defined as drug-related non-hematologic (Grade >/=3) or 
      hematologic (Grade 4) AEs. RESULTS: Sixteen patients were treated with 
      nintedanib; n = 4 for 150 mg bid, n = 12 for 200 mg bid. No DLTs were observed in 
      Cycle 1; therefore, the MTD was 200 mg bid. In subsequent cycles, two patients 
      had DLTs: renal failure and reduced blood magnesium levels. The most common AEs 
      were gastrointestinal. Three patients discontinued last study medication due to 
      AEs and one had a nintedanib dose reduction. No relevant PK interactions were 
      observed. Five patients had partial responses (31.3%) and eight had stable 
      disease (50.0%); disease control rate was 81.3%. There were three long-term 
      survivors (17-35 months). CONCLUSIONS: The safety profile of nintedanib 200 mg 
      bid plus cisplatin/gemcitabine was manageable, with AEs consistent with previous 
      observations. PK data demonstrated no interaction, and preliminary antitumor 
      activity was observed.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Forster, Martin
AU  - Forster M
AD  - Department of Oncology, University College London Cancer Institute, London, UK; 
      University College London Hospitals NHS Foundation Trust, London, UK.
FAU - Hackshaw, Allan
AU  - Hackshaw A
AD  - Cancer Research UK & UCL Cancer Trials Centre, University College London Cancer 
      Institute, London, UK.
FAU - De Pas, Tommaso
AU  - De Pas T
AD  - Medical Oncology Department, Istituto Europeo di Oncologia, Milan, Italy.
FAU - Cobo, Manuel
AU  - Cobo M
AD  - Medical Oncology Department, Hospital Universitario Malaga General FIMABIS, 
      Malaga, Spain.
FAU - Garrido, Pilar
AU  - Garrido P
AD  - Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, Spain.
FAU - Summers, Yvonne
AU  - Summers Y
AD  - Medical Oncology Department, Christie Hospital NHS Foundation Trust, Manchester, 
      UK.
FAU - Dingemans, Anne-Marie C
AU  - Dingemans AC
AD  - Department of Pulmonology, Maastricht University Medical Center, Maastricht, The 
      Netherlands.
FAU - Flynn, Michael
AU  - Flynn M
AD  - University College London Hospitals NHS Foundation Trust, London, UK.
FAU - Schnell, David
AU  - Schnell D
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - von Wangenheim, Ute
AU  - von Wangenheim U
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Loembe, Arsene-Bienvenu
AU  - Loembe AB
AD  - Boehringer Ingelheim B.V., Alkmaar, The Netherlands.
FAU - Kaiser, Rolf
AU  - Kaiser R
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; Institute of 
      Pharmacology, University of Mainz, Mainz, Germany.
FAU - Lee, Siow Ming
AU  - Lee SM
AD  - Department of Oncology, University College London Cancer Institute, London, UK; 
      University College London Hospitals NHS Foundation Trust, London, UK. Electronic 
      address: smlee@ucl.ac.uk.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180309
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Indoles)
RN  - 0W860991D6 (Deoxycytidine)
RN  - G6HRD2P839 (nintedanib)
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality
MH  - Cisplatin/*therapeutic use
MH  - Deoxycytidine/*analogs & derivatives/therapeutic use
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Indoles/*therapeutic use
MH  - Lung Neoplasms/*drug therapy/mortality
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Treatment Outcome
MH  - Gemcitabine
OTO - NOTNLM
OT  - Nintedanib
OT  - Non-small cell lung cancer
OT  - Squamous
EDAT- 2018/05/12 06:00
MHDA- 2019/07/23 06:00
CRDT- 2018/05/12 06:00
PHST- 2017/08/16 00:00 [received]
PHST- 2018/03/02 00:00 [revised]
PHST- 2018/03/08 00:00 [accepted]
PHST- 2018/05/12 06:00 [entrez]
PHST- 2018/05/12 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
AID - S0169-5002(18)30297-6 [pii]
AID - 10.1016/j.lungcan.2018.03.007 [doi]
PST - ppublish
SO  - Lung Cancer. 2018 Jun;120:27-33. doi: 10.1016/j.lungcan.2018.03.007. Epub 2018 
      Mar 9.