Pharmacokinetics and pharmacodynamics of melphalan in isolated limb infusion for recurrent localized limb malignancy

Isolated limb infusion (ILI) is an attractive, less complex alternative to Isolated limb perfusion (ILP). It has a lower morbidity in treating localiz ed recurrences and in transit metastases of the limb for tumours such as me lanoma, Merkel cell tumour and Kaposi's sarcoma, allowing administration of high concentrations of cytotoxic agent to the affected limb under hypoxic conditions. Melphalan is the preferred cytotoxic agent for the treatment of melanoma by ILP or ILI. We report pharmacokinetic data from 12 patients tr eated by ILI for tumours of the limb in Brisbane. The kinetics of drug dist ribution in the limb was calculated using a two-compartment vascular model, where both tissue and infusate act as well-stirred compartments. Analysis of melphalan concentrations in the perfusate during ILI showed good agreeme nt between the values measured and the concentrations predicted by the mode l. Recirculation and wash-out flow rates, tissue concentrations and the per meability surface area product (PS) were calculated. Correlations between t he PS value and the drug concentrations In the perfusate and tissue were su pported by the results. These data contribute to a better understanding of the distribution of melphalan during ILI in the limb, and offer the opportu nity to optimize the drug regimen for patients undergoing ILI. (C) 2001 Lip pincott Williams & Wilkins.