PMID- 25924991
OWN - NLM
STAT- MEDLINE
DCOM- 20160512
LR  - 20221207
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 33
IP  - 4
DP  - 2015 Aug
TI  - Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin 
      in Japanese patients with non-small-cell lung cancer.
PG  - 881-9
LID - 10.1007/s10637-015-0243-5 [doi]
AB  - BACKGROUND: Ipilimumab is an antibody that targets the cytotoxic T-lymphocyte 
      antigen-4 to potentiate an antitumor response. Adding ipilimumab 10 mg/kg to 
      paclitaxel (PTX) and carboplatin (CBDCA) in a phased schedule improved 
      progression-free survival in a phase II non-small-cell lung cancer (NSCLC) study. 
      METHODS: This dose-escalating, phase I study was designed to identify the 
      recommended dose of ipilimumab (3 or 10 mg/kg) by evaluating dose-limiting 
      toxicity (DLT; Cycles 3 and 4) in phased combination with PTX (175 mg/m(2)) and 
      CBDCA (area under the curve = 6) in Japanese patients with advanced NSCLC. 
      Treatment was administered intravenously every 3 weeks initially, followed by 
      some eligible patients receiving maintenance ipilimumab once every 12 weeks. 
      Additional endpoints included safety, tumor response, pharmacokinetics, and 
      immunogenicity. RESULTS: Fifteen patients were enrolled and 12 received 
      ipilimumab (n = 6, 3 mg/kg; n = 6, 10 mg/kg) in combination with PTX and CBDCA. 
      DLTs occurred in 2 patients (ipilimumab 3 mg/kg) and 1 patient (ipilimumab 10 
      mg/kg). The most common grade 3/4 adverse events (AEs) were decreased hemoglobin, 
      leukopenia, and neutropenia. The most common immune-related AEs affected the 
      skin, gastrointestinal, and nervous system. The safety profile was similar in 
      both cohorts. Three patients in each cohort achieved a partial response. The 
      pharmacokinetic (PK) profile of ipilimumab in Japanese patients was similar to 
      that observed in previous studies in non-Japanese patients. Conclusions The 
      recommended dose of ipilimumab in phased combination with PTX and CBDCA in 
      Japanese patients with NSCLC was identified as 10 mg/kg. The safety profile was 
      consistent with the previously defined AE profile.
FAU - Horinouchi, Hidehito
AU  - Horinouchi H
AD  - Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, 
      Chuo-ku, Tokyo, 104-0045, Japan, hhorinou@ncc.go.jp.
FAU - Yamamoto, Noboru
AU  - Yamamoto N
FAU - Fujiwara, Yutaka
AU  - Fujiwara Y
FAU - Sekine, Ikuo
AU  - Sekine I
FAU - Nokihara, Hiroshi
AU  - Nokihara H
FAU - Kubota, Kaoru
AU  - Kubota K
FAU - Kanda, Shintaro
AU  - Kanda S
FAU - Yagishita, Shigehiro
AU  - Yagishita S
FAU - Wakui, Hiroshi
AU  - Wakui H
FAU - Kitazono, Satoru
AU  - Kitazono S
FAU - Mizugaki, Hidenori
AU  - Mizugaki H
FAU - Tokudome, Takuto
AU  - Tokudome T
FAU - Tamura, Tomohide
AU  - Tamura T
LA  - eng
SI  - ClinicalTrials.gov/NCT01165216
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150501
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Ipilimumab)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/adverse effects/blood/pharmacokinetics/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacology/*therapeutic use
MH  - Asian People
MH  - Carboplatin/adverse effects/pharmacology/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism
MH  - Female
MH  - Humans
MH  - Ipilimumab
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Paclitaxel/adverse effects/pharmacology/*therapeutic use
MH  - Treatment Outcome
PMC - PMC4491360
EDAT- 2015/05/01 06:00
MHDA- 2016/05/14 06:00
PMCR- 2015/05/01
CRDT- 2015/05/01 06:00
PHST- 2015/02/17 00:00 [received]
PHST- 2015/04/15 00:00 [accepted]
PHST- 2015/05/01 06:00 [entrez]
PHST- 2015/05/01 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - 243 [pii]
AID - 10.1007/s10637-015-0243-5 [doi]
PST - ppublish
SO  - Invest New Drugs. 2015 Aug;33(4):881-9. doi: 10.1007/s10637-015-0243-5. Epub 2015 
      May 1.