TY - JOUR
T1 - Pharmacokinetics of isolated lung perfusion with melphalan for resectable pulmonary metastases, a phase I and extension trial
AU - Grootenboers, Marco Jj H.
AU - Hendriks, Jeroen M. H.
AU - van Boven, Wim J.
AU - Knibbe, Catherijne A. J.
AU - van Putte, Bart
AU - Stockman, Bernard
AU - de Bruijn, Ernst
AU - Vermorken, Jan B.
AU - van Schil, Paul E. Y.
AU - Schramel, Franz Mnh
PY - 2007
Y1 - 2007
N2 - 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
AB - 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
U2 - https://doi.org/10.1002/jso.20838
DO - https://doi.org/10.1002/jso.20838
M3 - Article
C2 - 17999399
SN - 0022-4790
VL - 96
SP - 583
EP - 589
JO - Journal of surgical oncology
JF - Journal of surgical oncology
IS - 7
ER -