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Efficacy and safety of recombinant human lymphotoxin‐α derivative with cisplatin and fluorouracil in patients with metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open‐label, controlled, phase 2b trial
Author(s) -
Wang Fenghua,
Wang Yun,
Sun Guoping,
Chen Jianhua,
Lin Yingcheng,
Liu Wei,
Zheng Rongsheng,
Chen Jia,
Zhang Helong,
Lan Haitao,
Qi Jun,
Liu Yangqing,
Deng Yanming,
Zhao Heng,
Xiong Jianping,
Xu Qing,
Jiang Wenqi,
Li Yuhong
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30845
Subject(s) - medicine , confidence interval , gastroenterology , fluorouracil , phases of clinical research , surgery , randomized controlled trial , oncology , chemotherapy
BACKGROUND Recombinant human lymphotoxin‐α derivative (rhLTα‐Da) is a lymphotoxin‐α derivative that is missing 27 N‐terminal amino acid residues. Previous studies indicated a benefit from the addition of rhLTα‐Da to cisplatin‐based treatment in patients with metastatic esophageal squamous cell carcinoma. The current study was conducted to evaluate the efficacy and safety of rhLTα‐Da plus cisplatin and fluorouracil (PF) in patients with mESCC. METHODS Patients from 15 centers in China were randomly assigned (1:1:1) to 3 arms (arm A, PF plus 10 μg/m 2 daily rhLTα‐Da; arm B, PF plus 20 μg/m 2 daily rhLTα‐Da; arm C, PF alone). The primary endpoints included progression‐free survival (PFS) and the confirmed overall response rate (ORR). An exploratory analysis was performed to evaluate the role of serum tumor necrosis factor receptor II (TNFR II) in predicting the efficacy of rhLTα‐Da. RESULTS Between September 2010 and May 2013, 150 patients were enrolled. No significant differences in either PFS or ORR were observed between the 3 arms. However, in a small subset of patients who had low serum TNFR II levels, the median PFS was significantly longer for those in arm B than for these in other 2 arms (7.2 months [95% confidence interval, 5.1‐8.6 months] for arm B vs 3.5 months [95% confidence interval, 1.7‐5.5 months] for arm A [ P = .022] and 4.0 months [95% confidence interval, 3.2‐6.3 months] for arm C [ P = .027]). The addition of rhLTα‐Da significantly increased the incidence of chills ( P < .001). CONCLUSIONS rhLTα‐Da combined with the PF regimen failed to improve PFS and ORR in patients with mESCC, except in a small subset that had low serum TNFR II concentrations. Cancer 2017;123:3986‐94 . © 2017 American Cancer Society .