Treatment of recurrent sarcoma of the extremities by isolated limb perfusion using tumor necrosis factor alpha and melphalan

Background: 24-60% of patients with soft tissue sarcoma shows local recurrences after treatment of the primary tumor. The event is associated with a high incidence of macroscopic or microscopic metastases and a poor survival. Our goal is to preserve a patient's functional limb by treating such cases with isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rHu TNF-alpha) and melphalan, which have demonstrated a potent antitumor activity in vivo and in vitro studies. Methods: During the period November 1991 to November 1995, 10 patients with unresectable recurrent soft tissue sarcoma of the limb were treated by ILP at intermediate hyperthermia (40-40.5 degrees C) with rHu TNF-alpha end melphalan. Two patients also received recombinant interferon gamma (rIFN-gamma) before and during ILP. We used a range of 2-4 mg for rHu TNF-alpha and 50-100 mg of melphalan. rIFN-gamma was administered on days -2 and -1 (15x10(6) IU) subcutaneously and the same dose was injected in the arterial line during ILP. Results: No perioperative surgical complication was observed. Local toxicity was moderate (grade I or II); general toxicity was observed in 6 patients (2 grade I and 4 grade III). Complete response was obtained in 7 cases; 2 patients had a partial response and finally 1 was a nonresponder and showed local progression, which required surgical amputation. Tumor necrosis (observed in 5 cases) was maximal in 4 patients (80-100%) and absent in the patient who had local progression. Conclusions: The results we obtained with the treatment of soft tissue sarcoma confirm the efficacy of ILP as a limb-sparing methodology for unresectable recurrences. Furthermore, rHu TNF-alpha and melphalan confirmed their antitumor activity when associated with hyperthermia. Amputation or disarticulation may be reliable as a second-choice treatment for these patients.