Pharmacokinetics of isolated lung perfusion with melphalan for resectable pulmonary metastases, a phase I and extension trial

Abstract Background: Isolated lung perfusion (ILuP) with melphalan was performed under normo- andhyperthermic conditions combined with pulmonary metastasectomy for patients withresectable lung metastases. We present the results of a phase I and extension trial developedto perform pharmacokinetic analysis. Methods: Twenty-one procedures of ILuP with melphalan were performed in the phase I trialaccording to a dose-escalation schedule under normothermic and hyperthermic conditionsfollowed by surgical resection of pulmonary metastases. In an extension trial, 8 additionalprocedures of ILuP with 15 and 45 mg melphalan were performed under hyperthermicconditions followed by pulmonary metastasectomy. Samples of serum, perfusate, lung andtumor tissue were obtained during and after the, in total, 29 procedures. Results: High perfusate concentrations of melphalan were recorded in contrast to lowsystemic concentrations, while marked interindividual variability was observed in melphalanconcentrations in perfusate, tumor and lung tissue. Statistically significant correlationsbetween melphalan dose and perfusate area under the concentration-time curve (R