Pharmacokinetics of the antineoplastic drug mitomycin C in regional chemotherapy using the aortic stop flow technique in advanced pancreatic carcinoma.
BACKGROUND
An isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects in comparison with systemic palliative chemotherapy. The aim of the present study was to investigate the pharmacokinetics of mitomycin C utilizing the aortic stop flow technique with commercially available tools in patients with advanced pancreatic carcinoma.


METHODS
Seventeen patients with unresectable or metastasized pancreatic carcinoma (diagnosed by histological investigation) underwent a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 mitomycin C (Mitomedac, medac, Hamburg, Germany) 22 times. Cytostatic concentration was determined intrainterventionally within the systemic and regional compartment.


RESULTS
The mitomycin C concentration was 10 times higher within the regional compared with the systemic compartment at its maximum. The area under the curve was 4.02 times greater. Toxicity was considerable, i.e. WHO grade I/II in 8 of 17 cases, and III/IV in 9 of 17 cases. Two treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission, 2 partial remissions). In 3 subjects, stable disease was registered, and in 11 individuals, tumor progression. The median survival was 4.1 months.


CONCLUSIONS
Though high concentrations of the cytostatic drug were achieved within the regional compartment, the aortic stop flow technique was associated with a high toxicity rate but no improvement of tumor response and survival in comparison with systemic chemotherapy. Despite its pharmacokinetic advantages, the aortic stop flow technique is currently not recommendable for routine use.
Meyer
Frank
F
Department of General Surgery, University Hospital, Magdeburg, Germany. frank.meyer@medizin.uni-magdeburg.de
Ridwelski
Karsten
K
Gebauer
Thomas
T
Grote
Reinhard
R
Martens-Lobenhoffer
Jens
J
Lippert
Hans
H
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D010478:Chemotherapy, Cancer, Regional Perfusion; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000009:adverse effects / Q000493:pharmacokinetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin