1. Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study.
- Author
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Jeong H, Kim BJ, Lee CK, Park I, Zang DY, Choi HJ, Lee SS, Park DH, Song TJ, Oh D, Moon SH, Kim KP, Wainberg Z, Ryoo BY, and Yoo C
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Liposomes, Adult, Progression-Free Survival, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Pancreatic Neoplasms mortality, Irinotecan therapeutic use, Irinotecan administration & dosage, Oxaliplatin administration & dosage, Oxaliplatin therapeutic use, Oxaliplatin adverse effects, Oxonic Acid administration & dosage, Oxonic Acid therapeutic use, Oxonic Acid adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Drug Combinations, Adenocarcinoma drug therapy, Adenocarcinoma secondary, Adenocarcinoma pathology, Adenocarcinoma mortality, Tegafur administration & dosage, Tegafur therapeutic use, Tegafur adverse effects
- Abstract
Introduction: This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma., Methods: Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0-1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D., Results: In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m
2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1-7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3-4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0-8.1) and median overall survival was 11.4 months (95 % CI, 9.8-15.5)., Conclusion: NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CY received honoraria from Servier, Bayer, AstraZeneca, Merck Sharp & Dohme, Eisai, Celgene, Bristol Myers Squibb, Ipsen, Novartis, Boryung Pharmaceuticals, Mundipharma, and Roche; and received research grants from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Ipsen, Boryung Pharmaceuticals, and Lunit Inc. C-kL received honoraria from AstraZeneca, Servier, Dong-A ST, Boryung Pharmaceuticals, Mundipharma, and Roche; consulting fees from Roche, and Daiichi Sankyo; and received research grants or supports from Ono Pharmaceuticals, Celltrion, Boryung Pharmaceuticals, GC Biopharma and Lunit Inc. ZW has received grants or contracts from Arcus and Bristol Myers Squibb, consulting fees from Amgen, Arcus, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Ipsen, Merck Sharp & Dohme, and Seagen, support for attending meetings or travel from Amgen, Bayer, and Merck Sharp & Dohme, and has participated on a data safety monitoring board or advisory board for Mirati and Pfizer. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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