Abstract

Tumor necrosis factor (TNF) induces rapid necrosis in a variety of experimental neoplasms. However, its clinical application is limited by life-threatening systemic toxicity. Isolated limb perfusion (ILP) enables administration of large doses of TNF and cytotoxic drugs directly to the affected limb, avoiding systemic toxicity. We describe our experience in 20 consecutive patients (10 with melanoma and 10 with soft tissue sarcoma) treated with high-dose TNF and melphalan via ILP. ILP was performed via the external iliac (10 cases), femoral (2), popliteal (5) or brachial (3) vessels. Patients received 3-4 mg TNF to an upper, and 1-1.5 mg/kg to a lower extremity. Isolation efficiency was determined by injection of radiolabelled albumin. The procedure was successful in all 20 patients. Local complications included wound infection in 6 cases and hematoma in 2. 1 patient developed sepsis secondary to extensive necrosis of a large, secondarily infected tumor. The first 6 patients who underwent high-flow perfusion experienced systemic side-effects, mainly hypotension. These side-effects were eliminated when low-flow perfusion was introduced. The response rate was 100%. In the sarcoma group, 5/10 had complete response, and 5 partial response. Amputation or mutilating surgery was avoided in 9/10. Of the 10 with melanoma, 7 had complete, and 3 partial response. We conclude that administration of TNF via ILP is a safe and effective modality for treating advanced neoplasms of the limbs.