Chemoembolization of lung metastases--pharmacokinetic behaviour of carboplatin in a rat model.
OBJECTIVE
To improve tumor control in lung metastases using a novel method: unilateral chemoembolization of the lung by instillation of degradable starch microspheres (DSM) and cytotoxic agents via the pulmonal artery.


METHODS
A rodent model of solitary metastasis (CC531 adenocarcinoma) was studied. The animals were randomized into three groups: the control group receiving carboplatin (45 mg/kg) intravenously, an isolated lung perfusion (ILP) group recieving buffered starch solution and carboplatin (15 mg/kg) and a third group receiving chemoembolization with carboplatin (15 mg/kg) and DSM (2 ml/kg). The total platinum concentration in serum, lung and lung tumor at defined times (15, 30, 60, 120 min) was measured using an inductively coupled plasma mass spectrometer (ICP-MS).


RESULTS
The area under concentration (AUC) versus time curves showed a 7.9- to 42.6-fold higher concentration in the tumor tissue comparing the ILP and chemoembolization group to the control group (p < 0.01). In the comparison of the AUCs of ILP versus chemoembolization, the tumor tissue of the lung showed a 5.4-fold higher concentration in the chemoembolization group (p < 0.01).


CONCLUSIONS
This is the first study to measure the concentration of carboplatin during chemoembolization of the lung. Compared to intravenous therapy, chemoembolization produced higher tumor tissue concentrations. Comparing chemoembolization to ILP, there was also an increase of carboplatin in the tumor tissue, without histological damage of the surrounding lung parenchyma.
Pohlen
Uwe
U
Department of Surgery, Charité Campus Benjamin Franklin Medical Center, Hindenburgdamm 30, D-12200 Berlin, Germany. Uwe.pohlen@charite.de
Rieger
Hayo
H
Meyer
Bernhard T
BT
Loddenkemper
Christoph
C
Buhr
Heinz J
HJ
Heitland
Peter
P
Koester
Helmut D
HD
Schneider
Paul
P
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects / Q000379:methods*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D008297:Male; D008863:Microspheres; D051381:Rats; D011919:Rats, Inbred Strains; D013213:Starch / Q000008:administration & dosage
D000970:Antineoplastic Agents; D013213:Starch; D016190:Carboplatin