Melphalan monitoring during hyperthermic perfusion of isolated limb for melanoma: pharmacokinetic study and 99mTc-albumin microcolloid technique

Background: The kinetics of melphalan leakage from extracorporeal fluid to the peripheral blood was studied in ten patients undergoing hyperthermic isolation perfusion of the lower limbs as an adjuvant treatment in high-fisk melanoma. Materials and Methods: Systemic leakage was monitored by a new technique using Tc-99m-albumin microcolloid. Serial samples were drawn from a peripheral vein and from the perfusion circuit during surgical treatment and analysed by HPLC. Results: The leakage measured with Tc-99m-albumin microcolloid ranged from 1.5 to 18 %/h (mean 8 %/h), The average concentrations in the perfusate were 200-300-fold those found in the systemic circulation. A good correlation (R=0.945) was obtained between systemic AUC (0 to 1 hour) and leakage measured through the Tc-99m procedure. Negligible toxicity was found and the survival rate yielded 92% of objective response. Conclusion: By studying the pharmacokinetic data of melphalan in the circuit and in the systemic circulation, we were able to validate the Tc-99m procedure used during clinical perfusion. Moreover, considering the efficiency of the system as well as the minimum toxicity and the high survival rate, a reduction of perfusion time may be considered.