Abstract
INTRODUCTION: Neoplastic fever (NF) is a relatively common yet frequently underrecognized complication in patients with advanced malignancies. NF is characterized by persistent low-grade fever (typically <38.5°C) driven by tumor-associated cytokine release rather than by infectious or autoimmune causes. As a leading contributor to fever of unknown origin in oncology patients, NF is often difficult to diagnose because of its nonspecific clinical presentation and reliance on exclusion criteria. This case illustrates the diagnostic complexity of NF and highlights the clinical value of targeted antipyretic strategies to support timely oncologic decision-making. CASE PRESENTATION: A 41-year-old male with stage IVC sigmoid colon adenocarcinoma presented with recurrent high-grade fever (up to 40.4°C), chills, and markedly elevated inflammatory markers (C-reactive protein [CRP]: 202.0 mg/L; procalcitonin: 3.44 ng/mL) over a 2-week period. Comprehensive infectious evaluations, including cultures, antigen testing, and imaging, were all negative. Empirical antibiotics and conventional nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, diclofenac) failed to achieve sustained defervescence. After ruling out infectious and autoimmune causes and considering chemotherapy-induced tumor lysis, NF was suspected. Administration of 500 mg of naproxen (suppository) led to rapid normalization of temperature (36.4°C) and sustained defervescence. A corresponding decrease in inflammatory markers (CRP: 51.6 mg/L; procalcitonin: 1.70 ng/mL) further confirmed the diagnosis. CONCLUSION: This case underscores the importance of NF in cancer patients with persistent high-grade fevers who are unresponsive to antimicrobial and standard antipyretic therapies and further demonstrates the distinctive efficacy of naproxen in managing such fevers compared with conventional NSAIDs. Specifically, the rapid and sustained defervescence observed following naproxen administration not only supported the diagnosis but also facilitated the timely continuation of anticancer treatment. Therefore, early recognition of NF and appropriate use of the naproxen test may help avoid unnecessary interventions and ultimately improve patient outcomes.