Management of NALIRIFOX

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NALIRIFOX implementation as a category 1 frontline option for locally advanced and metastatic pancreatic adenocarcinoma requires careful patient management strategies to optimize outcomes. Although NAPOLI-3 included only metastatic patients, treatment paradigms for locally advanced disease mirror those for stage IV disease, according to National Comprehensive Cancer Network guidelines. Patients with locally advanced disease may receive 4 to 6 months of NALIRIFOX followed by radiation consolidation (stereotactic body radiation therapy) if they demonstrate response and disease control, potentially converting some to surgical candidates.

The primary toxicities requiring proactive management include cytopenia and diarrhea, which represent the most common dose-limiting adverse effects. Cytopenia management involves aggressive use of growth factors, potentially prophylactically, to minimize febrile neutropenia risk and prevent treatment delays. Close monitoring of complete blood counts and prompt intervention with granulocyte colony-stimulating factors help maintain dose intensity and treatment schedules.

Diarrhea management requires comprehensive patient education, aggressive symptom control with antidiarrheal medications, and close monitoring to prevent advanced-grade toxicity leading to adverse outcomes. Most dose reductions and treatment holds in real-world practice result from diarrhea rather than other toxicities. Effective patient counseling on recognizing early symptoms, appropriate use of supportive medications, and when to contact health care providers is essential for successful NALIRIFOX administration and optimal patient outcomes.