Systemic and haemodynamic toxicity after isolated limb perfusion (ILP) with TNF-alpha

Area of Science:

• Oncology
• Pharmacology
• Cardiovascular Medicine

Background:

• Isolated limb perfusion (ILP) is a regional chemotherapy technique.
• Tumor necrosis factor alpha (TNF alpha) has been investigated for its anti-cancer properties.
• Understanding the systemic effects of ILP with TNF alpha is crucial for patient safety.

Purpose of the Study:

• To evaluate the systemic and hemodynamic effects of ILP with TNF alpha in patients with limb melanoma or sarcoma.
• To compare the toxicity of ILP with TNF alpha to Systemic Inflammatory Response Syndrome (SIRS).

Main Methods:

• A prospective study involving 17 patients with primary or recurrent limb tumors (melanoma or sarcoma).
• Patients underwent ILP with escalating doses of TNF alpha (0.5-2.0mg).
• Systemic and pulmonary hemodynamics were monitored using arterial catheters, with serial TNF alpha levels measured.

Main Results:

• Leakage of TNF alpha into systemic circulation occurred frequently, with high systemic concentrations observed.
• Two patients experienced severe toxicity (shock, respiratory failure) due to pulmonary edema.
• 14 patients developed a sepsis-like syndrome with hypoxia; 3 had pulmonary leaks.
• Hemodynamic changes included increased cardiac output (CO) and decreased systemic vascular resistance (SVR).
• All patients showed a reduction in hemoglobin (Hb).

Conclusions:

• ILP with TNF alpha induces significant cardiovascular, respiratory, and hematological toxicity.
• Hemodynamic changes resemble those seen in SIRS, likely due to TNF alpha leakage.
• Despite toxicity, side effects were reversible, with a mean ICU stay of 4 days.