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-α) 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 °C) with rHu TNF-α and melphalan. Two patients also received recombinant interferon gamma (rIFN-γ) before and during ILP. We used a range of 2-4 mg for rHu TNF-α and 50-100 mg of melphalan. rIFN-γ was administered on days -2 and -1 (15x106 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-α and melphalan confirmed their antitumor activity when associated with hyperthermia. Amputation or disarticulation may be reliable as a second-choice treatment for these patients.
Tumour necrosis factor alpha increases melphalan concentration in tumour tissue after isolated limb perfusion