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Isolated Perfusion of TNF-alpha Can Save Limbs

Isolated Perfusion of TNF-alpha Can Save Limbs

PARIS--Perfusion of an isolated limb with tumor necrosis factor
(TNF)- alpha and 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.

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