Toxicity and morbidity of isolated limb perfusion.

Because a relationship between toxicity and treatment outcome has never been demonstrated for isolated limb perfusion (ILP) with melphalan, it is important to keep the side-effects of the procedure restricted to a minimum. Risk factors for more severe acute regional toxicity have recently been identified with tissue temperature above 40 degrees C and a high melphalan peak concentration being the most important. Acute regional toxicity should be mild taking into account these factors and maintaining the normal physiological conditions in the limb during ILP. This should also decrease the incidence of long-term morbidity, especially ankle stiffness and muscle atrophy, since a relation between the severity of the acute regional tissue reactions and long-term morbidity has been demonstrated. Lymphedema is strongly linked to a concomitant regional lymph node dissection and this operation may be delayed until the acute regional tissue reactions have faded. It is not yet clear whether the addition of tumor necrosis factor-alpha (TNF-alpha) to melphalan increases regional toxicity. In the absence of melphalan leakage to the systemic circulation, systemic toxicity is minimal; this is also true with TNF-alpha. Compared to ILP with melphalan +/- TNF-alpha, ILP with other drugs is less effective and often is associated with increased regional toxicity.