| Autor: |
Pavlina Spiliopoulou, Farasat Kazmi, Francesca Aroldi, Thomas Holmes, David Thompson, Lucinda Griffiths, Cathy Qi, Matthew Parkes, Simon Lord, Gareth J. Veal, David J. Harrison, Vicky M. Coyle, Jill Graham, Thomas R. Jeffry Evans, Sarah P. Blagden |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Journal of Experimental & Clinical Cancer Research, Vol 43, Iss 1, Pp 1-16 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1756-9966 |
| DOI: |
10.1186/s13046-024-03010-1 |
| Popis: |
Abstract Purpose 5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU. Patients and methods NUC-3373 was administered as monotherapy to patients with advanced solid tumors refractory to standard therapy via intravenous infusion either on Days 1, 8, 15 and 22 (Part 1) or on Days 1 and 15 (Part 2) of 28-day cycles until disease progression or unacceptable toxicity. Primary objectives were maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) and schedule of NUC-3373. Secondary objectives included pharmacokinetics (PK), and anti-tumor activity. Results Fifty-nine patients received weekly NUC-3373 in 9 cohorts in Part 1 (n = 43) and 3 alternate-weekly dosing cohorts in Part 2 (n = 16). They had received a median of 3 prior lines of treatment (range: 0–11) and 74% were exposed to prior fluoropyrimidines. Four experienced dose-limiting toxicities: two Grade (G) 3 transaminitis; one G2 headache; and one G3 transient hypotension. Commonest treatment-related G3 adverse event of raised transaminases occurred in |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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