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: Feng-Hua Wang, Yun Wang, Zhen-Dong Chen, Jian-Hua Chen, Feng-Zhan Qin, Wen-Qi Jiang, Yu-Hong Li
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 33 Issue 11 Pg. 125 (Nov 2016) ISSN: 1559-131X [Electronic] United States
• PMID: 27743200 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Cisplatin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, pathology)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Cisplatin (administration & dosage, adverse effects)
• Esophageal Neoplasms (drug therapy, pathology)
• Esophageal Squamous Cell Carcinoma
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Male
• Middle Aged
• Recombinant Proteins (administration & dosage, adverse effects, genetics)
• Stomach Neoplasms (drug therapy, pathology)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (administration & dosage, genetics)