Yang, Muh-HwaMuh-HwaYangWu, Shang-YinShang-YinWuHo, I-WeiI-WeiHoChiang, Nai-JungNai-JungChiangHsaio, Chin-FuChin-FuHsaioLin, Chen-YuanChen-YuanLinLien, Ming-YuMing-YuLienChang, Peter Mu-HsinPeter Mu-HsinChangChen, Jia-HongJia-HongChenHsieh, Ching-YunChing-YunHsiehRUEY-LONG HONGLee, Chao-TungChao-TungLeeChen, Li-TzongLi-TzongChenLiu, Tsang-WuTsang-WuLiuChiu, Chang-FangChang-FangChiuBai, Li-YuanLi-YuanBai2026-01-302026-01-302025-10https://scholars.lib.ntu.edu.tw/handle/123456789/735672To evaluate the efficacy and safety of nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with platinum-refractory or intolerant head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC).In this multicenter, phase 2 study (NCT03712397), patients with advanced HNSCC (n = 43) or ESCC (n = 16) who had failed or were intolerant to platinum-based chemotherapy received biweekly nal-IRI 80 mg/m (equivalent to 70 mg/m of irinotecan base), LV 400 mg/m, and 5-FU 2400 mg/m until progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR).In the intent-to-treat analysis, the ORR and disease control rate were 8.5% and 59.3% for the entire group. In the HNSCC subgroup, ORR and disease control rate were 11.6% and 65.1%, with a median progression-free survival (PFS) of 2.7 months and an overall survival (OS) of 8.1 months. By contrast, no objective responses were observed in ESCC (ORR 0%, disease control rate 43.8%, median OS 4.2 months). The most common grade 3/4 toxicities were lymphopenia (50.8%), neutropenia (42.4%), leukopenia (33.9%), anemia (28.8%), and anorexia (8.5%).Nal-IRI/5-FU/LV demonstrates modest activity with acceptable safety profiles in patients with platinum-refractory or intolerable advanced HNSCC. The exploratory findings warrant confirmation in larger, randomized studies.ClinicalTrials.gov: NCT03712397.enesophageal cancerhead and neck cancernanoliposomal irinotecanplatinumsquamous cell carcinomajournal article10.1002/cam4.7130741117518