Background: In a prior randomized phase II trial comparing hyperthermic isolated limb perfusion (HILP) with four different doses of tumor necrosis factor alpha (TNF-alpha), no dose effect was detected for response, but systemic toxicity was far lower with low-dose TNF-alpha. The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-alpha.
Methods: We assessed a prospective database comprising 100 HILP (38-40 degrees C) with melphalan (10 mg/L) and TNF-alpha (1 mg). The remnant tumor was resected 2 months later.
Results: Among 52 recurrences, 18 were in a previously irradiated field. Stages according to the American Joint Committee on Cancer classification were II (19 patients), III (78 patients), and IV (3 patients). The site/size were: 30 patients/57 mm and 70 patients/86 mm for the upper and lower limbs, respectively. Tumor grades (FNCLCC) were 1 (23 patients), 2 (34 patients), and 3 (43 patients). Fifty-one patients had received systemic chemotherapy before HILP. Responses on magnetic resonance imaging were 30% complete, 49% partial, 9% no change, and 12% progression. No mortality or systemic toxicity occurred. Local toxicity (Wieberdink) attained grade 2 (16 patients), 3 (5 patients), and 4 (1 patient). Limbs were able to be saved in 87% patients. Three-year overall survival and the local recurrence rate were 89% and 18%, respectively. Age, sex, tumor size, recurrence, uni- or multifocality, grade, preoperative chemotherapy, and a previously irradiated field were not predictive of response or local toxicity.
Conclusions: We confirm that 1 mg of TNF-alpha is as effective as the standard dose and results in no systemic toxicity.