PMID- 28950288
OWN - NLM
STAT- MEDLINE
DCOM- 20171004
LR  - 20240210
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 117
IP  - 7
DP  - 2017 Sep 26
TI  - SELECT-3: a phase I study of selumetinib in combination with platinum-doublet 
      chemotherapy for advanced NSCLC in the first-line setting.
PG  - 938-946
LID - 10.1038/bjc.2017.271 [doi]
AB  - BACKGROUND: We investigated selumetinib (AZD6244, ARRY-142886), an oral, potent, 
      and highly selective, allosteric MEK1/2 inhibitor, plus platinum-doublet 
      chemotherapy for patients with advanced/metastatic non-small cell lung cancer. 
      METHODS: In this Phase I, open-label study (NCT01809210), treatment-naive 
      patients received selumetinib (50, 75, 100 mg BID PO) plus standard doses of 
      gemcitabine or pemetrexed plus cisplatin or carboplatin. Primary objectives were 
      safety, tolerability, and determination of recommended Phase II doses. RESULTS: 
      Fifty-five patients received treatment: selumetinib 50 or 75 mg plus 
      gemcitabine/cisplatin (n=10); selumetinib 50 mg plus gemcitabine/carboplatin 
      (n=9); selumetinib 50, 75 or 100 mg plus pemetrexed/carboplatin (n=21); 
      selumetinib 75 mg plus pemetrexed/cisplatin (n=15). Most frequent adverse events 
      (AEs) were fatigue, nausea, diarrhoea and vomiting. Grade ⩾3 selumetinib-related 
      AEs were reported in 30 (55%) patients. Dose-limiting toxicities (all n=1) were 
      Grade 4 anaemia (selumetinib 75 mg plus gemcitabine/cisplatin), Grade 4 
      thrombocytopenia/epistaxis and Grade 4 thrombocytopenia (selumetinib 50 mg plus 
      gemcitabine/carboplatin), Grade 4 febrile neutropenia (selumetinib 100 mg plus 
      pemetrexed/carboplatin), and Grade 3 lethargy (selumetinib 75 mg plus 
      pemetrexed/cisplatin). Partial responses were confirmed in 11 (20%) and 
      unconfirmed in 9 (16%) patients. CONCLUSIONS: Standard doses of 
      pemetrexed/carboplatin or pemetrexed/cisplatin were tolerated with selumetinib 
      75 mg BID. The selumetinib plus gemcitabine-containing regimens were not 
      tolerated.
FAU - Greystoke, Alastair
AU  - Greystoke A
AD  - Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK.
FAU - Steele, Nicola
AU  - Steele N
AD  - The Beatson West of Scotland Cancer Centre, Glasgow, UK.
FAU - Arkenau, Hendrik-Tobias
AU  - Arkenau HT
AD  - Sarah Cannon Research Institute UK, London, UK.
AD  - University College London, London, UK.
FAU - Blackhall, Fiona
AU  - Blackhall F
AD  - The Christie Hospital NHS Foundation Trust, Manchester, UK.
FAU - Md Haris, Noor
AU  - Md Haris N
AD  - Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK.
FAU - Lindsay, Colin R
AU  - Lindsay CR
AD  - The Beatson West of Scotland Cancer Centre, Glasgow, UK.
FAU - Califano, Raffaele
AU  - Califano R
AD  - The Christie Hospital NHS Foundation Trust, Manchester, UK.
FAU - Voskoboynik, Mark
AU  - Voskoboynik M
AD  - Sarah Cannon Research Institute UK, London, UK.
FAU - Summers, Yvonne
AU  - Summers Y
AD  - The Christie Hospital NHS Foundation Trust, Manchester, UK.
FAU - So, Karen
AU  - So K
AD  - AstraZeneca, Cambridge, UK.
FAU - Ghiorghiu, Dana
AU  - Ghiorghiu D
AD  - AstraZeneca, Cambridge, UK.
FAU - Dymond, Angela W
AU  - Dymond AW
AD  - AstraZeneca, Macclesfield, UK.
FAU - Hossack, Stuart
AU  - Hossack S
AD  - Covance, Leeds, UK.
FAU - Plummer, Ruth
AU  - Plummer R
AD  - Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK.
FAU - Dean, Emma
AU  - Dean E
AD  - The Christie Hospital NHS Foundation Trust, Manchester, UK.
LA  - eng
GR  - 20465/CRUK_/Cancer Research UK/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170824
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (AZD 6244)
RN  - 0 (Benzimidazoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 04Q9AIZ7NO (Pemetrexed)
RN  - 0W860991D6 (Deoxycytidine)
RN  - BG3F62OND5 (Carboplatin)
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anemia/chemically induced
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/*adverse 
      effects
MH  - Benzimidazoles/administration & dosage/adverse effects
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Chemotherapy-Induced Febrile Neutropenia/etiology
MH  - Cisplatin/administration & dosage
MH  - Deoxycytidine/administration & dosage/analogs & derivatives
MH  - Diarrhea/chemically induced
MH  - Epistaxis/chemically induced
MH  - Fatigue/chemically induced
MH  - Female
MH  - Humans
MH  - Lethargy/chemically induced
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Nausea/chemically induced
MH  - Pemetrexed/administration & dosage
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects
MH  - Thrombocytopenia/chemically induced
MH  - Vomiting/chemically induced
MH  - Gemcitabine
PMC - PMC5625674
COIS- AG received consultancy fees from AstraZeneca. KS, DG and AWD are employees of 
      AstraZeneca, and DG and AWD hold stock options. FB received a grant and personal 
      fees from, and is a Board Member for AstraZeneca. NS has received travel costs 
      from AstraZeneca for her attendance at AstraZeneca-funded meetings. RC, RP and YS 
      have received honorarium for advisory boards from AstraZeneca. H-TA, NMD, CRL, SH 
      and MV have no conflicts of interest to declare.
EDAT- 2017/09/28 06:00
MHDA- 2017/10/05 06:00
PMCR- 2017/09/26
CRDT- 2017/09/27 06:00
PHST- 2016/12/23 00:00 [received]
PHST- 2017/05/26 00:00 [revised]
PHST- 2017/07/20 00:00 [accepted]
PHST- 2017/09/27 06:00 [entrez]
PHST- 2017/09/28 06:00 [pubmed]
PHST- 2017/10/05 06:00 [medline]
PHST- 2017/09/26 00:00 [pmc-release]
AID - bjc2017271 [pii]
AID - 10.1038/bjc.2017.271 [doi]
PST - ppublish
SO  - Br J Cancer. 2017 Sep 26;117(7):938-946. doi: 10.1038/bjc.2017.271. Epub 2017 Aug 
      24.