Pre-clinical evaluation of the activity of gemcitabine as a basis for regional chemotherapy of pancreatic and colorectal cancer.
OBJECTIVE
To estimate the potential activity of gemcitabine for hepatic arterial infusion (HAI) chemotherapy in pancreatic and colorectal cancer.


METHODS
The anti-proliferative effects of gemcitabine were determined in MIA PaCa-2 and PMH2/89 pancreatic and HT29 and NMG64/84 colon cancer cell lines and in fresh tumours from patients with liver metastases of colon, rectal and pancreatic cancer in vitro using the human tumour colony forming assay.


RESULTS
Gemcitabine showed concentration and time-dependent cytotoxic effects in all tested cell lines. The IC(50)of gemcitabine in MIA PaCa-2, PMH2/89, HT29 and NMG64/84 cells at 2 h exposure time were >100, 18, 100 and 2.5 microg/ml, respectively, at 4 h 15, 1.2, 45 and 0.5 microg/ml, respectively, and at 24 h 0.2, 0.1, 1.8 and 0.1 microg/ml, respectively. All tumours displayed concentration dependent inhibition of colony formation after exposure to gemcitabine for 2 h. The IC(50)values of gemcitabine in six of the 10 metastases were </=100 microg/ml.


CONCLUSIONS
Based on our results and theoretical considerations regarding hepatic arterial infusion therapy gemcitabine seems to be suitable for HAI therapy phase II studies. Moreover, patients with colorectal or pancreatic tumours that demonstrated in vivo sensitivity may benefit from regional chemotherapy with gemcitabine.
Kornmann
M
M
Department of General Surgery, University of Ulm, Germany.
Butzer
U
U
Blatter
J
J
Beger
H G
HG
Link
K H
KH
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007700:Kinetics; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine