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.

Feng-Hua Wang, Yun Wang, Guo-Ping Sun, Jian-Hua Chen, Ying-Cheng Lin, Wei Liu, Rong-Sheng Zheng, Jia Chen, He-Long Zhang, Hai-Tao Lan, Jun Qi, Yang-Qing Liu, Yan-Ming Deng, Heng Zhao, Jian-Ping Xiong, Qing Xu, Wen-Qi Jiang, Yu-Hong Li

Journal: Cancer 2017;123(20):3986-3994

PMID: 28640389

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Abstract

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 daily rhLTα-Da; arm B, PF plus 20 μg/m 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.

Address: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.; Department of Medical Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.; Department of Medical Oncology, Hunan Cancer Hospital, Changsha, People's Republic of China.; Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, People's Republic of China.; Department of Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.; Department of Medical Oncology, Anhui Provincial Cancer Hospital, Bengbu, People's Republic of China.; Department of Oncology, Jiangsu Cancer Hospital, Nanjing, People's Republic of China.; Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.; Department of Oncology, Sichuan Provincial People's Hospital, Chengdu, People's Republic of China.; Department of Thoracic Surgery, Chongqing Cancer Hospital, Chongqing, People's Republic of China.; Department of Medical Oncology, Huai'an First People's Hospital, Huai'an, People's Republic of China.; Department of Medical Oncology, First People's Hospital of Foshan, Foshan, People's Republic of China.; Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.; Department of Oncology, First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.; Department of Oncology, Shanghai 10th People's Hospital, Shanghai, People's Republic of China.

DOI: 10.1002/cncr.30845

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MeSH Terms: Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Squamous Cell, China, Cisplatin, Disease-Free Survival, Esophageal Neoplasms, Female, Fluorouracil, Humans, Lymphotoxin-alpha, Male, Middle Aged, Receptors, Tumor Necrosis Factor, Type II, Recombinant Proteins