Pre-clinical evaluation of the activity of gemcitabine as a basis for regional chemotherapy of pancreatic and colorectal cancer

Aims: 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 IC50of gemcitabine in MIA PaCa-2, PMH2/89, HT29 and NMG64/84 cells at 2 h exposure time were >100, 18, 100 and 2.5 μg/ml, respectively, at 4 h 15, 1.2, 45 and 0.5 μg/ml, respectively, and at 24 h 0.2, 0.1, 1.8 and 0.1 μg/ml, respectively. All tumours displayed concentration dependent inhibition of colony formation after exposure to gemcitabine for 2 h. The IC50values of gemcitabine in six of the 10 metastases were ≤100 μg/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 demonstratedin vivo sensitivity may benefit from regional chemotherapy with gemcitabine.