PARIS--Perfusion of an isolated limb with tumor necrosis factor (TNF)- alpha and melphalan(Drug information on melphalan) (Alkeran) can avoid amputation in more than 80% of patients with nonresectable soft tissue sarcomas of the extremities, Alexander Eggermont, MD, PhD, reported at the Sixth International Congress on Anti-Cancer Treatment (ICACT).
TNF-alpha may work by stimulating the immune system, but its main target is the endothelial cells of tumor vessels. "TNF-alpha has been used in patients with sarcoma and melanoma, but any tumor with a decent vascular bed should respond," said Dr. Eggermont, of the Daniel den Hoed Cancer Clinic, Rotterdam.
Extremely High Doses
He explained that, by connecting the main vein and artery of the limb to a heart-lung machine and applying a tourniquet, the limb can be exposed to extremely high doses of the two agents--doses that would be toxic if given systemically.
"With this type of delivery system, you can deliver to the tumor drug concentrations that are 20- to 50-fold the concentrations reached when the two drugs are administered intravenously," Dr. Egger-mont said. "This is true dose intensification," he added.
Dr. Eggermont stressed that, realistically speaking, the goal of the procedure is to preserve the limb rather than prolong survival, since most of these patients have grade III sarcomas, a quarter have multiple tumors, and more than a quarter have systemic metastases at the time of limb perfusion.
The 125 patients in this multicenter European trial received TNF-alpha, 3 mg (for lesions in the arm) or 4 mg (for lesions in the leg), for 90 minutes at a temperature of 38° to 39°C, with 10 to 13 mg/L of mel-phalan added for the last 60 minutes of the infusion.
Although the first 55 patients had been primed with subcutaneous interferon-gamma, the investigators have since dispensed with this pretreatment regimen.