TNF-alpha and doxorubicin in hyperthermic perfusion for limb sarcomas

Eighteen patients, subdivided into groups of three, were perfused for 90 min with escalating doses of TNF-alpha (0.5-3.3 mg) and standard doses of doxorubicin (bolus 0.7-1.4 mg/kg) at a tumor temperature of at least 41 degrees C, with the aim to ascertain the maximum tolerable dose (MTD) and the activity of TNF-alpha combined with doxorubicin in hyperthermic antiblastic perfusion (HAP) for patients with limb sarcomas, candidates for amputation. Tumor response was assessed both pathologically and radiologically. Severe systemic toxicity (WHO) was observed in only 2 patients. Locoregional toxicity (Wieberdink's) was grade I in 3 patients, grade II or III in 10 and grade IV in 5. A strict correlation between the TNF dosage and the grade of limb reaction was found, grade IV being retrieved only with TNF dose >1 mg and/or muscular temperature >41.5 degrees C. Tumor necrosis was evaluated in 16 patients: in 11 (68.8%) it scored more than 75% while in 5 it was 25 to 75%. Four cases (25%) had 100% tumor histological necrosis. Limb sparing surgery was feasible in 13 (81%). Our findings suggest that this is a well-tolerated and highly active regimen in HAP.