PMID- 29136201
OWN - NLM
STAT- MEDLINE
DCOM- 20180330
LR  - 20221207
IS  - 1465-3621 (Electronic)
IS  - 0368-2811 (Linking)
VI  - 48
IP  - 1
DP  - 2018 Jan 1
TI  - Safety and tolerability of selumetinib as a monotherapy, or in combination with 
      docetaxel as second-line therapy, in Japanese patients with advanced solid 
      malignancies or non-small cell lung cancer.
PG  - 31-42
LID - 10.1093/jjco/hyx144 [doi]
AB  - OBJECTIVE: This Phase I study (NCT01605916) investigated the safety, tolerability 
      and pharmacokinetic profile of selumetinib plus docetaxel as second-line therapy 
      in Japanese patients with locally advanced or metastatic non-small cell lung 
      cancer (NSCLC), or selumetinib monotherapy in Japanese patients with advanced 
      solid malignancies. METHODS: All enrolled patients received single-dose 
      selumetinib 25, 50 or 75 mg, followed by a 3-day washout. Combination therapy 
      cohorts then started a 21-day cycle of docetaxel 60 mg/m2 plus selumetinib 25 or 
      75 mg twice-daily (BID) on Day 1. Thereafter, selumetinib BID continued for 20 
      days; patients received </=6 cycles. Following single-dosing, monotherapy cohorts 
      underwent a 21-day cycle of selumetinib 25, 50 or 75 mg BID. RESULTS: 
      Thirty-three patients were enrolled and 25 assigned to treatment (combination, n 
      = 8; monotherapy, n = 17). Most frequent adverse events (AEs) included: vomiting, 
      decreased appetite, diarrhea, nausea and stomatitis (combination cohorts); 
      gastrointestinal disorders, skin and subcutaneous tissue disorders (monotherapy 
      cohorts). Grade 3 dose-limiting toxicities: febrile neutropenia, causally related 
      to combination therapy (n = 3); pneumonitis, selumetinib 50 mg monotherapy (n = 
      1). Selumetinib 75 mg monotherapy and selumetinib 25 mg plus docetaxel 60 mg/m2 
      were tolerated; selumetinib 75 mg plus docetaxel 60 mg/m2 was not tolerated. 
      Selumetinib pharmacokinetic profile was similar when administered as a 
      monotherapy or in combination with docetaxel. CONCLUSIONS: Selumetinib 75 mg 
      monotherapy was tolerated in Japanese patients with NSCLC. Due to the overall 
      selumetinib AE profile, the maximum tolerated dose was not determined for 
      combination therapy or monotherapy. Selumetinib 75 mg BID plus docetaxel 60 mg/m2 
      was not tolerated in this patient population.
CI  - (c) The Author 2017. Published by Oxford University Press. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Seto, Takashi
AU  - Seto T
AD  - Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka.
FAU - Hirai, Fumihiko
AU  - Hirai F
AD  - Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka.
FAU - Saka, Hideo
AU  - Saka H
AD  - Department of Medical Oncology and Respiratory Medicine, National Hospital 
      Organisation Nagoya Medical Centre, Nagoya.
FAU - Kogure, Yoshihito
AU  - Kogure Y
AD  - Department of Medical Oncology and Respiratory Medicine, National Hospital 
      Organisation Nagoya Medical Centre, Nagoya.
FAU - Yoh, Kiyotaka
AU  - Yoh K
AD  - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa.
FAU - Niho, Seiji
AU  - Niho S
AD  - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa.
FAU - Fukase, Kenjiro
AU  - Fukase K
AD  - Research and Development, AstraZeneca K. K., Osaka, Japan.
FAU - Shimada, Hitoshi
AU  - Shimada H
AD  - Research and Development, AstraZeneca K. K., Osaka, Japan.
FAU - Sasai, Michitaka
AU  - Sasai M
AD  - Research and Development, AstraZeneca K. K., Osaka, Japan.
FAU - Fukino, Koichi
AU  - Fukino K
AD  - Research and Development, AstraZeneca K. K., Osaka, Japan.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - England
TA  - Jpn J Clin Oncol
JT  - Japanese journal of clinical oncology
JID - 0313225
RN  - 0 (AZD 6244)
RN  - 0 (Benzimidazoles)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - *Asian People
MH  - Benzimidazoles/*adverse effects/pharmacokinetics/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Demography
MH  - Docetaxel
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Taxoids/pharmacokinetics/*therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - *Japanese
OT  - *docetaxel
OT  - *non-small cell lung cancer
OT  - *pharmacokinetics
OT  - *selumetinib
EDAT- 2017/11/15 06:00
MHDA- 2018/03/31 06:00
CRDT- 2017/11/15 06:00
PHST- 2017/06/26 00:00 [received]
PHST- 2017/10/27 00:00 [accepted]
PHST- 2017/11/15 06:00 [pubmed]
PHST- 2018/03/31 06:00 [medline]
PHST- 2017/11/15 06:00 [entrez]
AID - 4614430 [pii]
AID - 10.1093/jjco/hyx144 [doi]
PST - ppublish
SO  - Jpn J Clin Oncol. 2018 Jan 1;48(1):31-42. doi: 10.1093/jjco/hyx144.