Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma
| Autor: | Jialin Tang, Jing Huang, Xingyuan Wang, Jianping Xu, Yun Liu, Bo Zhang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Neutropenia Esophageal Neoplasms Maximum Tolerated Dose medicine.medical_treatment Irinotecan Toxicology Gastroenterology Esophageal squamous cell carcinoma 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) In patient Adverse effect Pharmacology Chemotherapy Leukopenia Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Phase i study 030104 developmental biology Oncology 030220 oncology & carcinogenesis Liposomes Liposomal Irinotecan Original Article Female Esophageal Squamous Cell Carcinoma Topoisomerase I Inhibitors medicine.symptom business Febrile neutropenia medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose This phase I trial was performed to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), preliminary efficacy, and pharmacokinetics (PK) of LY01610, a novel liposome-encapsulated irinotecan, in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods This trial was conducted in two stages. In the dose-escalation stage, patients with advanced ESCC refractory or intolerant to previous chemotherapy received escalating doses of LY01610. A recommended dose based on patient tolerance was then expanded in the second stage. LY01610 was administered intravenously every 2 weeks, except that the first cycle in dose escalation was 3 weeks to allow observation of DLTs. Results Twenty-four patients were enrolled across 4 dose levels (30, 60, 90 and 120 mg/m2). The DLTs included vomiting and febrile neutropenia, and the MTD was 90 mg/m2. The most common grade 3/4 adverse events were leukopenia in six patients (25.0%), anemia in six patients (25.0%) and neutropenia in five patients (20.8%). One patient achieved complete response, and four had partial response, including one patient receiving LY01610 at the starting dose of 30 mg/m2. Compared with conventional irinotecan, the PK profile of LY01610 was characterized by increased and prolonged exposure of total irinotecan and the active metabolite SN-38 in plasma. Conclusion LY01610 demonstrated manageable toxicity and promising anti-tumor activity in patients with advanced ESCC. Future clinical development of LY01610 as single agent or in combination with other anti-cancer agents in treating ESCC patients is warranted. Trial registration NCT04088604 at ClinicalTrials.gov. Supplementary Information The online version contains supplementary material available at 10.1007/s00280-021-04294-2. |
| Databáze: | OpenAIRE |
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