Reduction of drug leakage by negative-balance isolated pelvic perfusion: correlation between leakage and in-out flow rate in a pig model.
OBJECTIVE
Isolated pelvic perfusion (IPP) therapy exposes target tissues to high doses of anticancer drugs with low systemic concentrations, but the major drawback is drug leakage into the systemic circulation, which often thwarts the increased drug concentration. In this study, the efficacy of altering the in-out flow rate during IPP in order to decrease the leakage was assessed in adult pigs.


METHODS
The abdominal aorta and the infrarenal vena cava were occluded with two balloon catheters, blood in the extracorporeal circuit was circulated with twin rotary pumps, and the IPP was performed with platinum. Three sets of in-out flow rates were used, and the degree of drug leakage into the systemic circulation was evaluated. The volume of blood withdrawn was equal to the volume returned (300 ml/min; group A), 5% higher (group B), or 10% higher (group C). The platinum concentrations in the pelvic circulation, systemic circulation, and urine were measured and compared.


RESULTS
The average and maximum plasma platinum concentrations in the pelvic circulation did not significantly differ among the three groups. The plasma platinum concentrations in the systemic venous circulation of the three groups significantly (P<0.01) decreased as the volume withdrawn during IPP increased. The percentage of platinum eliminated in the urine during IPP was significantly (P<0.01) lower in group B and C than in group A.


CONCLUSIONS
Setting the volume withdrawn higher than the volume returned decreased leakage into the systemic circulation under isolated pelvic perfusion.
Murata
Satoru
S
Department of Radiology/Center for Advanced Medical Technology, Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo, 113-8602, Japan. murata_satoru@nms.ac.jp
Tajima
Hiroyuki
H
Kusakai
Gen-ichi
G
Kumazaki
Tatsuo
T
Abe
Yutaka
Y
Onozawa
Shiro
S
Komada
Yasushige
Y
Kondo
Yukihiro
Y
Kimata
Ryoji
R
Himeno
Seiichiro
S
Satake
Mitsuo
M
D000792:Angiography; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D001775:Blood Circulation; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D008297:Male; D008954:Models, Biological; D010388:Pelvis / Q000098:blood supply*; D010984:Platinum / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D012039:Regional Blood Flow; D013552:Swine
D000970:Antineoplastic Agents; D010984:Platinum