title: A phase IIa study of rhLTα-Da in combination with cisplatin and fluorouracil for patients with metastatic esophageal squamous cell carcinoma or gastric adenocarcinoma.
abstract: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative missing 27 N-terminal amino acid residues. This multicenter phase IIa trial was conducted to evaluate the safety, efficacy and pharmacokinetics of rhLTα-Da with cisplatin (DDP) and 5-fluorouracil (5-Fu) for metastatic esophageal squamous cell cancer (ESCC) and gastric adenocarcinoma (GC). Two different rhLTα-Da doses (10 µg/m2/d and 20 µg/m2/d) in combination with DDP and 5-Fu were evaluated in this study. The first 6 ESCC and 6 GC patients were given 10 µg/m2/d rhLTα-Da followed by DDP (15 mg/m2/d) and 5-Fu (750 mg/m2/d) on days 1-5. The next 6 ESCC and 6 GC patients were given 20 µg/m2/d rhLTα-Da after fewer than 2 of the 6 patients who received the 10 µg/m2/d dose exhibited dose-limiting rhLTα-Da-related toxicities. The treatment was 21 days a cycle until a maximum of 6. The rhLTα-Da pharmacokinetic analyses were performed. Twelve ESCC and 12 GC patients were enrolled. The toxicities were controllable and reversible. The most common adverse events related to rhLTα-Da were chills (37.5 %, 9/24) and fever (16.7 %, 4/24) (all grades 1-2). The overall response rates in the 10- and 20-µg/m2/d groups were 50 % (6/12) and 33.3 % (4/12), respectively, and the overall response rates of the ESCC and GC patients were 66.7 % (8/12) and 16.7 % (2/12), respectively. rhLTα-Da in combination with DDP and 5-Fu exhibited a tolerable toxicity profile. The addition of rhLTα-Da may enhance the anti-tumor efficacy of platinum-based chemotherapy in metastatic ESCC.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.|Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.|Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Second Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, The Affiliated Tumor Hospital of Bengbu Medical College, Bengbu, People's Republic of China.
authors.forename: Feng-Zhan
authors.initials: FZ
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.|Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Wen-Qi
authors.initials: WQ
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. liyh@sysucc.org.cn.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. liyh@sysucc.org.cn.|Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China. liyh@sysucc.org.cn.|State Key Laboratory of Oncology in South China and Department of Medical Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, 651# Dongfeng Road East, Guangzhou, 510060, People's Republic of China. liyh@sysucc.org.cn.
authors.forename: Yu-Hong
authors.identifier: http://orcid.org/0000-0002-5710-9096
authors.initials: YH
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-fluorouracil; Cisplatin; Esophageal cancer; Gastric cancer; Lymphotoxin-α; Metastases