Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy.

PURPOSE: To define the maximum tolerated dose (MTD) of hepatic intraarterial chemotherapy with gemcitabine, administered with and without starch microspheres, in patients with inoperable intrahepatic cholangiocarcinomas and liver metastases of pancreatic carcinomas.

METHODS: Gemcitabine was administered on days 1 and 8 with intervals of 2 weeks between the cycles. In group A the initial gemcitabine dose of 1,000 mg/m(2) (without microspheres) was increased in 200-mg/m(2) steps up to a maximum dose of 2,000 mg/m(2). In group B the MTD with microspheres was assessed by giving an additional microsphere dose according to tumor extent and body weight, increasing gemcitabine starting from a dose-step below the MTD with microspheres. The MTD was evaluated via clinical and laboratory findings.

RESULTS: Twenty-four patients were enrolled (12 males, 12 females, mean age 59.17 years; intrahepatic cholangiocarcinoma: n = 17, liver metastases of pancreatic carcinoma: n = 7). The MTD of gemcitabine without microspheres was reached at 1,400 mg/m(2), and of gemcitabine with microspheres at 1,800 mg/m(2). The comparative evaluation revealed statistically significant better data for the time to progression (p < 0.01) and survival for the group with microspheres (6.8 and 20.2 months) in comparison to the group without microspheres (4.2 and 13.5 months).

CONCLUSION: This clinical study indicates that the intraarterial application of gemcitabine with doses higher than the recommended 1,000 mg/m(2) is well tolerated if combined with microspheres, and yields respectable results in patients who do not respond to systemic chemotherapy.