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Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma

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...

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Autores principales: Liu, Yun, Zhang, Bo, Xu, Jianping, Wang, Xingyuan, Tang, Jialin, Huang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143070/
https://www.ncbi.nlm.nih.gov/pubmed/34031756
http://dx.doi.org/10.1007/s00280-021-04294-2
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author Liu, Yun
Zhang, Bo
Xu, Jianping
Wang, Xingyuan
Tang, Jialin
Huang, Jing
author_facet Liu, Yun
Zhang, Bo
Xu, Jianping
Wang, Xingyuan
Tang, Jialin
Huang, Jing
author_sort Liu, Yun
collection PubMed
description 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/m(2)). The DLTs included vomiting and febrile neutropenia, and the MTD was 90 mg/m(2). 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/m(2). 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.
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spelling pubmed-81430702021-05-25 Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma Liu, Yun Zhang, Bo Xu, Jianping Wang, Xingyuan Tang, Jialin Huang, Jing Cancer Chemother Pharmacol Original Article 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/m(2)). The DLTs included vomiting and febrile neutropenia, and the MTD was 90 mg/m(2). 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/m(2). 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. Springer Berlin Heidelberg 2021-05-24 2021 /pmc/articles/PMC8143070/ /pubmed/34031756 http://dx.doi.org/10.1007/s00280-021-04294-2 Text en © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Liu, Yun
Zhang, Bo
Xu, Jianping
Wang, Xingyuan
Tang, Jialin
Huang, Jing
Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma
title Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma
title_full Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma
title_fullStr Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma
title_full_unstemmed Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma
title_short Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma
title_sort phase i study of liposomal irinotecan (ly01610) in patients with advanced esophageal squamous cell carcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143070/
https://www.ncbi.nlm.nih.gov/pubmed/34031756
http://dx.doi.org/10.1007/s00280-021-04294-2
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