How to manage fever of malignancy?

Management of Fever of Malignancy

Naproxen is the most effective treatment for fever of malignancy and should be used as first-line therapy at a dose of 250-600 mg orally every 8-12 hours. 1

Initial Assessment and Diagnosis

• Fever of malignancy (neoplastic fever) is defined as fever arising solely as a manifestation of malignancy, after excluding infectious causes
• Diagnostic approach:
  • Complete infectious workup including blood cultures, urine cultures, and chest X-ray
  • Empiric antibiotics may be initiated if infection cannot be ruled out immediately
  • Consider naproxen as a diagnostic test: complete lysis of fever within 24 hours suggests neoplastic fever 2

Treatment Algorithm

First-line therapy:

1. Naproxen 250-600 mg orally every 8 hours
   • Most effective NSAID for neoplastic fever with 80-90% response rate 1
   • Complete lysis typically occurs within 12-24 hours
   • Initial dose of 600 mg/day appears most appropriate 3

Alternative options if naproxen is contraindicated:

1. Other NSAIDs:

   • Diclofenac 75 mg IV (brief infusion)
   • Indomethacin 50-75 mg orally every 6 hours 4

2. Non-NSAID antipyretics:

   • Acetaminophen (paracetamol) 650 mg orally every 4 hours (scheduled, not PRN)
   • Metamizol 2500 mg IV (where available) 5
   • Propacetamol 2000 mg IV (brief infusion) 5

Management of Associated Symptoms

• Rigors/chills:

  • Meperidine 25-50 mg IV every 4 hours as needed
  • Hydromorphone 0.5 mg IV every 15 minutes as needed (may repeat up to 3 doses) 4

• Hypotension (if present):

  • Administer normal saline or lactated Ringer's 250-500 mL IV bolus over 30-60 minutes
  • Repeat blood pressure check 30 minutes post-bolus
  • If hypotension persists, consider additional 250 mL IV bolus 4

Monitoring and Follow-up

• Continue naproxen for 5-7 days for symptomatic relief 2
• Monitor for:
  • Temperature response (expect complete lysis within 24 hours)
  • Improvement in malaise and fatigue
  • Potential side effects of NSAIDs (GI discomfort, renal dysfunction)
  • Recurrence of fever if medication is discontinued

Special Considerations

• Fever may recur when naproxen is discontinued (observed in 70% of patients) 1
• For long-term management, consider continuing naproxen for 1-2 months if well-tolerated 3
• If fever persists despite naproxen therapy for 24 hours, reconsider diagnosis and resume infectious workup 2
• NSAIDs should be used with caution in patients with:
  • Renal dysfunction (serum creatinine >2 mg/dL)
  • Decreased urine output
  • Thrombocytopenia (platelets <50,000/μL) 4

Mechanism of Action

Neoplastic fever is mediated by cytokines (TNF, IL-1, IL-6, IFN) produced by host macrophages or tumor cells, which stimulate prostaglandin production affecting the hypothalamic thermoregulatory center. NSAIDs block this pathway by inhibiting cyclooxygenase, explaining their superior efficacy compared to acetaminophen in managing neoplastic fever 6.