PMID- 35116396
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220501
IS  - 2219-6803 (Electronic)
IS  - 2218-676X (Print)
IS  - 2218-676X (Linking)
VI  - 10
IP  - 2
DP  - 2021 Feb
TI  - Phase 1 dose-escalation study of apatinib and irinotecan in esophageal squamous 
      cell carcinoma patients.
PG  - 627-636
LID - 10.21037/tcr-20-2492 [doi]
AB  - BACKGROUND: Apatinib, an inhibitor of vascular endothelial growth factor receptor 
      (VEGFR), has been used to treat esophagogastric adenocarcinoma. However, the 
      dosage of apatinib varies greatly in clinical practice, and its safety in 
      esophageal squamous cell carcinoma (ESCC) patients is unclear. Therefore, we 
      initiated a phase 1 dose-escalation trial to identify the maximum tolerated dose 
      (MTD) of apatinib when combined with irinotecan in ESCC. METHODS: The trial had a 
      standard 3+3 design. The dosage of irinotecan was fixed at 150 mg/m(2) repeated 
      every 2 weeks, while the daily dosage of apatinib was escalated from 250 mg, to 
      500 mg, to 750 mg. Dose-limiting toxicity (DLT) was defined as grade 4 
      hematological or grade 3-4 non-hematological adverse events (AEs). RESULTS: 
      Twelve patients were enrolled. Three DLTs occurred, comprising a grade 3 perianal 
      abscess and a grade 3 case of kaliopenia in the level 3 cohort, and a grade 4 
      leukopenia in the level 2 cohort. Based on these DLTs, the MTD of apatinib was 
      500 mg daily. The most common AEs were leukopenia (91.7%), fatigue (91.7%), 
      anemia (66.7%), and diarrhea (58.3%). One case of grade 2 hematochezia and one 
      case of grade 2 subclavian vein thrombosis were observed. In the nine evaluable 
      cases, the disease control rate (DCR) was 66.7% (6/9). The median 
      progression-free and overall survival (OS) times were 3.6+/-1.2 and 6.6+/-3.4 months, 
      respectively. CONCLUSIONS: This phase 1 dose-escalation trial showed that, when 
      combined with irinotecan, a daily dose of 500 mg apatinib was the optimum dose to 
      treat ESCC.
CI  - 2021 Translational Cancer Research. All rights reserved.
FAU - Jia, Jun
AU  - Jia J
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), the VIP-II Gastrointestinal Cancer Division of the Medical 
      Department, Peking University Cancer Hospital & Institute, Beijing, China.
FAU - Yu, Jing
AU  - Yu J
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), the VIP-II Gastrointestinal Cancer Division of the Medical 
      Department, Peking University Cancer Hospital & Institute, Beijing, China.
FAU - Sun, Zhiwei
AU  - Sun Z
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), the VIP-II Gastrointestinal Cancer Division of the Medical 
      Department, Peking University Cancer Hospital & Institute, Beijing, China.
FAU - Yang, Ying
AU  - Yang Y
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), the VIP-II Gastrointestinal Cancer Division of the Medical 
      Department, Peking University Cancer Hospital & Institute, Beijing, China.
FAU - Liu, Chuanling
AU  - Liu C
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), the VIP-II Gastrointestinal Cancer Division of the Medical 
      Department, Peking University Cancer Hospital & Institute, Beijing, China.
FAU - Xiao, Yanjie
AU  - Xiao Y
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), the VIP-II Gastrointestinal Cancer Division of the Medical 
      Department, Peking University Cancer Hospital & Institute, Beijing, China.
FAU - Zhang, Xiaodong
AU  - Zhang X
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), the VIP-II Gastrointestinal Cancer Division of the Medical 
      Department, Peking University Cancer Hospital & Institute, Beijing, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Cancer Res
JT  - Translational cancer research
JID - 101585958
PMC - PMC8798775
OTO - NOTNLM
OT  - Apatinib
OT  - esophageal squamous cell carcinoma (ESCC)
OT  - maximum tolerated dose (MTD)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/tcr-20-2492). The authors have no 
      conflicts of interest to declare.
EDAT- 2022/02/05 06:00
MHDA- 2022/02/05 06:01
PMCR- 2021/02/01
CRDT- 2022/02/04 05:48
PHST- 2020/07/09 00:00 [received]
PHST- 2020/12/17 00:00 [accepted]
PHST- 2022/02/04 05:48 [entrez]
PHST- 2022/02/05 06:00 [pubmed]
PHST- 2022/02/05 06:01 [medline]
PHST- 2021/02/01 00:00 [pmc-release]
AID - tcr-10-02-627 [pii]
AID - 10.21037/tcr-20-2492 [doi]
PST - ppublish
SO  - Transl Cancer Res. 2021 Feb;10(2):627-636. doi: 10.21037/tcr-20-2492.