Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan

Open Access
Publisher Website
Google Scholar
Abstract
Background. Utilization of alpha‐tumor necrosis factor (α‐TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of α‐TNF by isolation perfusion in extracorporeal circulation. Methods. From December 1991 to November 1992, 14 patients underwent perfusion with α‐TNF (2–4 mg, total dose), gamma‐interferon (1.5 × 106 IU), and melphalan (10 mg/1/perfused limb). Twelve patients presented intransit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38–40.5°C, muscle temperature). Results. Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic‐like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan‐failure syndrome, likely due to α‐TNF. The follow‐up time ranges from 4 to 15 months (median, 6). Conclusions. The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.