Phase II study on neoadjuvant hyperthermic-antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas.

BACKGROUND

Locoregional control of soft tissue sarcomas of the limbs is achieved generally using a multidisciplinary approach consisting of conservative surgery combined with radiation therapy, intraarterial chemotherapy, or hyperthermic antiblastic perfusion (HAP). Before surgery, HAP seems to be the more suitable tool in decreasing tumor mass and allowing limb-sparing surgery. The authors' aim was to ascertain the activity of HAP with doxorubicin against intermediate or high grade limb tumors.

METHODS

In 23 patients with limb sarcomas (2 patients International Union Against Cancer Stage IIA, 4 stage IIB, 1 stage IIIA, 11 stage IIIB, and 5 stage IVB) doxorubicin was administered via HAP 4-6 weeks before surgery. The drug (bolus, 0.7-1.4 mg/kg) was perfused for 60 minutes with a tumor temperature of at least 40.5 degrees C (range, 40.5-42.6 degrees). Tumor necrosis was then assessed radiologically and pathologically.

RESULTS

Systemic toxicity was hematologic grade (G) 2 in 2 patients, gastrointestinal (hepatic) in 6, G1 in 2, G2 in 3, and G3 in 1; 2 patients had alopecia; locoregional toxicity (graded according to Wieberdink) was G1 or G2 in 18, G3 in 4, and G4 in 1. Tumor necrosis was more than 50% in 17 patients (74%). Limb-sparing surgery was feasible in 20 patients (91%). At present, 14 patients are alive. Six had local recurrences, and eight had distant metastases.

CONCLUSIONS

Our findings show that HAP with doxorubicin is an active and well-tolerated procedure within a multidisciplinary approach to treatment of limb sarcomas.