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Pharmacokinetics of isolated lung perfusion with melphalan for resectable pulmonary metastases, a phase I and extension trial
Author(s) -
Grootenboers Marco JJ H.,
Hendriks Jeroen M.H.,
van Boven Wim J.,
Knibbe Catherijne A.J.,
van Putte Bart,
Stockman Bernard,
De Bruijn Ernst,
Vermorken Jan B.,
Van Schil Paul E.Y.,
Schramel Franz MNH
Publication year - 2007
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20838
Subject(s) - melphalan , medicine , perfusion , pharmacokinetics , lung , urology , area under the curve , chemotherapy
Background Isolated lung perfusion (ILuP) with melphalan was performed under normo‐ and hyperthermic conditions combined with pulmonary metastasectomy for patients with resectable lung metastases. We present the results of pharmacokinetic analysis of a phase I and extension trial. Methods Twenty‐one procedures of ILuP with melphalan were performed in the phase I trial according to a dose‐escalation schedule under normothermic and hyperthermic conditions followed by surgical resection of pulmonary metastases. In an extension trial 8 additional procedures with 15 and 45 mg melphalan were performed under hyperthermic conditions. Samples of serum, perfusate, lung, and tumor tissue were obtained. Results High perfusate concentrations of melphalan were recorded in contrast to low systemic concentrations. Marked interindividual variability was observed in melphalan concentrations in perfusate, tumor, and lung tissue. Statistically significant correlation between melphalan dose, and perfusate area under the concentration–time curve (R 2 = 0.578, P = 0.001) and lung tissue concentrations (R 2 = 0.459, P = 0.028) were noted. No significant correlation between melphalan dose and tumor tissue concentrations could be established. Conclusion Isolated lung perfusion effectively delivers high doses of melphalan to the lung and tumor tissues with minimal systemic levels. Significant correlation between perfused melphalan dose, perfusate area under the concentration–time curve and lung tissue melphalan concentrations were observed. J. Surg. Oncol. 2007;96:583–589. © 2007 Wiley‐Liss, Inc.