PMID- 34699693
OWN - NLM
STAT- MEDLINE
DCOM- 20220201
LR  - 20231105
IS  - 2523-3548 (Electronic)
IS  - 2523-3548 (Linking)
VI  - 42
IP  - 1
DP  - 2022 Jan
TI  - Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus 
      cisplatin in the first-line treatment of locally advanced or metastatic lung 
      squamous cell carcinoma: A multicenter, randomized, open-label, parallel 
      controlled clinical study.
PG  - 3-16
LID - 10.1002/cac2.12225 [doi]
AB  - BACKGROUND: Lipusu is the first commercialized liposomal formulation of 
      paclitaxel and has demonstrated promising efficacy against locally advanced lung 
      squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a 
      multicenter, randomized, phase 3 study to compare the efficacy and safety of 
      cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line 
      treatment in locally advanced or metastatic LSCC. METHODS: Patients enrolled were 
      aged between 18 to 75 years, had locally advanced (clinical stage IIIB, 
      ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) 
      LSCC, had no previous systemic chemotherapy and at least one measurable lesion as 
      per the Response Evaluation Criteria in Solid Tumors (version 1.1) before 
      administration of the trial drug. The primary endpoint was progression-free 
      survival (PFS). The secondary endpoints included objective response rate (ORR), 
      disease control rate (DCR), overall survival (OS), and safety profiles. To 
      explore the possible predictive value of plasma cytokines for LP treatment, 
      plasma samples were collected from the LP group at baseline and first efficacy 
      evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 
      1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The 
      correlation between treatment outcomes and dynamic changes in the levels of 
      cytokines were evaluated in preliminary analyses. RESULTS: The median duration of 
      follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the 
      GP group were included in the per protocol set (PPS). In the PPS, the median PFS 
      was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, 
      P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the 
      LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) 
      and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP 
      group. A significantly lower proportion of patients in the LP group experienced 
      adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 
      0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of 
      cytokine levels in the LP group showed that low baseline levels of 27 cytokines 
      were associated with an increased ORR, and 15 cytokines were associated with 
      improved PFS, with 14 cytokines, including TNF-alpha, IFN-gamma, IL-6, and IL-8, 
      demonstrating an overlapping trend. CONCLUSION: The LP regimen demonstrated 
      similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced 
      or metastatic LSCC but had more favorable toxicity profiles. The study also 
      identified a spectrum of different cytokines that could be potentially associated 
      with the clinical benefit in patients who received the LP regimen.
CI  - (c) 2021 The Authors. Cancer Communications published by John Wiley & Sons 
      Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer 
      Institute, Tongji University School of Medicine, Shanghai, 200433, P. R. China.
FAU - Pan, Yueyin
AU  - Pan Y
AD  - Department of Chemotherapy, Anhui Provincial Hospital, Hefei, Anhui, 230001, P. 
      R. China.
FAU - Shi, Qin
AU  - Shi Q
AD  - Department of Oncology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, Fujian, 
      350008, P. R. China.
FAU - Zhang, Guojun
AU  - Zhang G
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, Henan, 450052, P. R. China.
FAU - Jiang, Liyan
AU  - Jiang L
AD  - Department of Respiration, Shanghai Chest Hospital, Shanghai Jiao Tong 
      University, Shanghai, 200030, P. R. China.
FAU - Dong, Xiaorong
AU  - Dong X
AD  - Cancer Center, Union Hospital of Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan, Hubei, 430022, P. R. China.
FAU - Gu, Kangsheng
AU  - Gu K
AD  - Department of Medical Oncology, the First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, 230032, P. R. China.
FAU - Wang, Huijuan
AU  - Wang H
AD  - Department of Respiration, Henan Cancer Hospital, Zhengzhou, Henan, 450008, P. R. 
      China.
FAU - Zhang, Xiaochun
AU  - Zhang X
AD  - Department of Medical Oncology, the Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, 266000, P. R. China.
FAU - Yang, Nong
AU  - Yang N
AD  - Department of Medical Oncology, Hunan Cancer Hospital, Changsha, Hunan, 410013, 
      P. R. China.
FAU - Li, Yuping
AU  - Li Y
AD  - Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital 
      of Wenzhou Medical College, Shangcai village, Wenzhou, Zhejiang, 325000, P. R. 
      China.
FAU - Xiong, Jianping
AU  - Xiong J
AD  - Department of Medical Oncology, the First Affiliated Hospital 
      of Nanchang University, Nanchang, Jiangxi, 330006, P. R. China.
FAU - Yi, Tienan
AU  - Yi T
AD  - Department of Medical Oncology, Xiang Yang Central Hospital, Xiangyang, Hubei, 
      441021, P. R. China.
FAU - Peng, Min
AU  - Peng M
AD  - Department of Medical Oncology, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, 430060, P. R. China.
FAU - Song, Yong
AU  - Song Y
AD  - Department of Respiration, General Hospital of Eastern Theater Command of Chinese 
      People's Liberation Army, Nanjing, Jiangsu, 210002, P. R. China.
FAU - Fan, Yun
AU  - Fan Y
AD  - Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 
      310022, P. R. China.
FAU - Cui, Jiuwei
AU  - Cui J
AD  - Cancer Center, the First Bethune Hospital of Jilin University, Changchun, Jilin, 
      130021, P. R. China.
FAU - Chen, Gongyan
AU  - Chen G
AD  - Department of Medical Oncology, Harbin Medical University Cancer Hospital, 
      Harbin, Heilongjiang, 150081, P. R. China.
FAU - Tan, Wei
AU  - Tan W
AD  - Department of Respiratory Medicine, Weifang People's Hospital, Weifang, Shandong, 
      261000, P. R. China.
FAU - Zang, Aimin
AU  - Zang A
AD  - Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, 
      Hebei, 071030, P. R. China.
FAU - Guo, Qisen
AU  - Guo Q
AD  - Department of Internal Medicine, Shandong Cancer Hospital & Institute, Jinan, 
      Shandong, 250117, P. R. China.
FAU - Zhao, Guangqiang
AU  - Zhao G
AD  - Department of Thoracic Surgery,  the Third Affiliated Hospital of Kunming Medical 
      University, Kunming, Yunnan, 650118, P. R. China.
FAU - Wang, Ziping
AU  - Wang Z
AD  - Department of Medical Oncology, Beijing Cancer Hospital, Beijing, 100142, P. R. 
      China.
FAU - He, Jianxing
AU  - He J
AD  - Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of 
      Guangzhou Medical University, Guangzhou, Guangdong, 510120, P. R. China.
FAU - Yao, Wenxiu
AU  - Yao W
AD  - Department of Chemotherapy, Sichuan Cancer Hospital & Institute, Chengdu, 
      Sichuan, 610041, P. R. China.
FAU - Wu, Xiaohong
AU  - Wu X
AD  - Department of Medical Oncology, the Fourth People's Hospital of Wuxi, Wuxi, 
      Jiangsu, 214062, P. R. China.
FAU - Chen, Kai
AU  - Chen K
AD  - Department of Medical Oncology, the First Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu, 215006, P. R. China.
FAU - Hu, Xiaohua
AU  - Hu X
AD  - Department of Medical Oncology, the First Affiliated Hospital of Guangxi Medical 
      University, Nanning, Guangxi, 530021, P. R. China.
FAU - Hu, Chunhong
AU  - Hu C
AD  - Department of Medical Oncology, the Second Xiangya Hospital of Central South 
      University, Changsha, Hunan, 410011, P. R. China.
FAU - Yue, Lu
AU  - Yue L
AD  - Department of Medical Oncology, Qingdao Municipal Hospital, Qingdao, Shandong, 
      266071, P. R. China.
FAU - Jiang, Da
AU  - Jiang D
AD  - Department of Medical Oncology, the 4th Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, 050010, P. R. China.
FAU - Wang, Guangfa
AU  - Wang G
AD  - Department of Respiratory Medicine, Peking University First Hospital, Beijing, 
      100034, P. R. China.
FAU - Liu, Junfeng
AU  - Liu J
AD  - Department of Thoracic Surgery, the 4th Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, 050010, P. R. China.
FAU - Yu, Guohua
AU  - Yu G
AD  - Department of Medical Oncology, Weifang People's Hospital, Weifang, Shandong, 
      261000, P. R. China.
FAU - Li, Junling
AU  - Li J
AD  - Cancer Hospital Chinese Academy of Medical Sciences, Beijing, 100021, P. R. 
      China.
FAU - Bai, Jianling
AU  - Bai J
AD  - Department of Biostatistics, School of Public Health, Nanjing Medical University, 
      Nanjing, Jiangsu, 211166, P. R. China.
FAU - Xie, Wenmin
AU  - Xie W
AD  - Nanjing Luye Pharmaceutical Co., Ltd, Nanjing, Jiangsu, 210061, P. R. China.
FAU - Zhao, Weihong
AU  - Zhao W
AD  - Nanjing Luye Pharmaceutical Co., Ltd, Nanjing, Jiangsu, 210061, P. R. China.
FAU - Wu, Lihong
AU  - Wu L
AD  - Genecast Biotechnology Co., Ltd, Wuxi, Jiangsu, 214104, P. R. China.
FAU - Zhou, Caicun
AU  - Zhou C
AD  - Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer 
      Institute, Tongji University School of Medicine, Shanghai, 200433, P. R. China.
LA  - eng
SI  - ClinicalTrials.gov/NCT02996214
GR  - 2017ZZ02012/Nanjing Luye Pharmaceutical Co. Ltd, Nanjing, China/
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211026
PL  - United States
TA  - Cancer Commun (Lond)
JT  - Cancer communications (London, England)
JID - 101723675
RN  - 0 (Liposomes)
RN  - 0W860991D6 (Deoxycytidine)
RN  - P88XT4IS4D (Paclitaxel)
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Carcinoma, Squamous Cell/drug therapy
MH  - Cisplatin/adverse effects
MH  - Deoxycytidine/analogs & derivatives
MH  - Humans
MH  - Liposomes
MH  - Lung
MH  - *Lung Neoplasms/drug therapy
MH  - Middle Aged
MH  - Paclitaxel/adverse effects
MH  - Young Adult
MH  - Gemcitabine
PMC - PMC8753311
OTO - NOTNLM
OT  - chemotherapy
OT  - cisplatin
OT  - clinical trial
OT  - gemcitabine
OT  - liposomal paclitaxel (Lipusu)
OT  - locally advanced
OT  - lung squamous cell carcinoma
OT  - metastatic
OT  - multicenter
OT  - plasma cytokines
EDAT- 2021/10/27 06:00
MHDA- 2022/02/02 06:00
PMCR- 2021/10/26
CRDT- 2021/10/26 17:34
PHST- 2021/09/02 00:00 [revised]
PHST- 2021/04/28 00:00 [received]
PHST- 2021/09/23 00:00 [accepted]
PHST- 2021/10/27 06:00 [pubmed]
PHST- 2022/02/02 06:00 [medline]
PHST- 2021/10/26 17:34 [entrez]
PHST- 2021/10/26 00:00 [pmc-release]
AID - CAC212225 [pii]
AID - 10.1002/cac2.12225 [doi]
PST - ppublish
SO  - Cancer Commun (Lond). 2022 Jan;42(1):3-16. doi: 10.1002/cac2.12225. Epub 2021 Oct 
      26.