Naproxen Test Protocol for Fever of Unknown Origin in Malignancy
The naproxen test is a highly effective diagnostic tool for differentiating neoplastic fever from infectious fever in cancer patients, with a response rate of 80-90% when administered at an appropriate dose of 500-600 mg per day.
Protocol for Naproxen Test
Patient Selection
- Patients with cancer and fever of undetermined origin (temperature ≥38.3°C)
- Fever persisting for at least 3-7 days
- No obvious source of infection on physical examination
- Negative blood and urine cultures
- Negative chest radiograph for pneumonia
- Consider after failure of empiric antibiotic therapy (typically 3+ days)
Administration Protocol
Dosage: Naproxen 250-300 mg orally every 8 hours (total 600-900 mg/day)
- Alternative: Naproxen 375 mg orally every 12 hours for 3 days 1
Monitoring:
- Record temperature every 4-6 hours
- Monitor for excessive sweating (common with lysis of neoplastic fever)
- Assess subjective improvement in malaise and fatigue
Interpretation:
- Positive test: Complete or partial lysis of fever within 24 hours
- Complete response: Temperature decreases to ≤37.0°C
- Partial response: Temperature decreases ≥1.0°C but remains >37.0°C
- Negative test: No significant temperature reduction within 24 hours
- Positive test: Complete or partial lysis of fever within 24 hours
Clinical Significance
- Positive test (fever resolves): Strongly suggests neoplastic fever 2
- Negative test (fever persists): Suggests infectious etiology or other causes 2
Precautions and Contraindications
High-Risk Patients
Renal toxicity risk: Age >60 years, compromised fluid status, interstitial nephritis, concomitant nephrotoxic drugs 3
- Monitor: BUN, creatinine (discontinue if values double)
GI toxicity risk: Age >60 years, history of peptic ulcer disease, significant alcohol use 3
- Consider gastroprotection with proton pump inhibitors
Cardiac toxicity risk: History of cardiovascular disease, concurrent anticoagulants 3
- Monitor blood pressure (discontinue if hypertension develops/worsens)
Hematologic concerns: Use with caution in thrombocytopenia (platelets <50,000/μL) 4
Monitoring During Test
- Baseline: Blood pressure, BUN, creatinine, liver function tests, CBC, fecal occult blood
- Continue monitoring for adverse effects during test period
Follow-up Management
If Test Positive (Neoplastic Fever)
- Continue naproxen for symptomatic relief (5-7 days or longer if needed) 5
- Proceed with appropriate cancer therapy
- Consider limiting extensive fever workups and prolonged empiric antibiotics 5
If Test Negative (Likely Infectious)
- Discontinue naproxen
- Continue/expand infectious disease workup
- Consider infectious disease consultation 3
Clinical Pearls
- Fever typically recurs within 3 days after naproxen discontinuation if the underlying neoplastic cause remains untreated 6
- The test has high specificity for neoplastic fever (nearly 100% in some studies) 2
- Partial responses may be seen in fever from connective tissue diseases 2
- Consider alternative diagnoses such as malignancies, infectious diseases, and other inflammatory disorders if results are equivocal 3
The naproxen test provides a simple, cost-effective approach to differentiate neoplastic from infectious fever in cancer patients, potentially avoiding unnecessary antibiotics and invasive diagnostic procedures while guiding appropriate therapeutic interventions.