Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusion.

BACKGROUND

Of the different options for limb-sparing treatment for patients with soft tissue limb sarcomas (STLS), hyperthermic antiblastic perfusion (HAP) combined with surgery might be the most effective in terms of tumor resectability, local control, and aesthetic and functional results. The aim of this study was to identify the most safe, active, and effective perfusional regimen in order to improve multidisciplinary treatment for patients with advanced STLS.

METHODS

The first trial undertaken (which involved 18 patients) was a Phase I study to assess the maximum tolerable dose of doxorubicin, the second (with 29 patients) was a Phase II study of HAP with doxorubicin, and the third (with 20 patients) was a Phase I-II study to assess the maximum tolerable dose and tumor response to doxorubicin combined with tumor necrosis factor (TNF). Statistical tests were performed on the whole series to evaluate the factors influencing local toxicity, tumor response, and local disease free and overall survival.

RESULTS

Grade IV systemic toxicity was observed in only 2 cases (TNF >1 mg). Muscle temperature (>41.5 degrees C) was the limiting factor for locoregional toxicity. Limb-sparing surgery was feasible for 60 patients (92.3%). The highest tumor response was observed in the third trial, with complete histologic necrosis in 26.3% of cases. Muscle and tumor temperature (>41.5 degrees C) and the type of trial had a statistically significant influence on response. The local recurrence rate was influenced by tumor site, type of trial, maximum tumor temperature, and local toxicity, whereas the overall survival was influenced by the presence of metastasis, tumor grade, and response to treatment.

CONCLUSIONS

These findings show that HAP with doxorubicin and TNF (< or =1 mg) at a muscle temperature of < or =41.5 degrees C is a safe, active, and effective perfusional regimen for the multidisciplinary treatment of patients with advanced STLS.