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.
Eur J Cancer
; 208: 114194, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38968872
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/m2 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.Palabras clave
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Ácido Oxónico
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Neoplasias Pancreáticas
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Adenocarcinoma
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Protocolos de Quimioterapia Combinada Antineoplásica
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Tegafur
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Combinación de Medicamentos
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Irinotecán
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Oxaliplatino
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2024
Tipo del documento:
Article