Phase Ib trial of gemcitabine with yttrium-90 in patients with hepatic metastasis of pancreatobiliary origin

Nariman Nezami, Juan C. Camacho, Nima Kokabi, Bassel F. El-Rayes, Hyun S. Kim


Background: Gemcitabine, a chemotherapy for hepatic metastasis with pancreatic cancer (PC) or intrahepatic cholangiocarcinoma (ICC) origin, may radiosensitize the targeted tumor cells for yttrium-90 radioembolization (90Y-RE). This clinical trial was designed to investigate the effects of a combination of 90Y-RE and gemcitabine in hepatic metastasis of PC or ICC origin.
Methods: Fourteen patients who had histopathologic diagnosis of unresectable hepatic metastasis of PC or ICC origin were enrolled into the open-label phase Ib clinical trial. Induction dose of gemcitabine on day 1 was followed by 90Y-RE on day 2 with predetermined doses of gemcitabine to follow till week 12. Maximal tolerated dose (MTD) of gemcitabine in combination with 90Y-RE, associated toxicities and hepatic progression free survival (HPFS) were assessed. The tumor response rate was evaluated using both RECIST and PERCIST criteria.
Results: Eight patients met the study criteria; three with PC and five with ICC. The mean age of the patients was 69.4 years. Seven out of 8 patients tolerated predetermined gemcitabine regime (dose level 1 at 400 mg/m2 and dose level 2 at 600 mg/m2). All of the patients developed grade 1 toxicities. Three patients (37.5%) had grade 2 hepatobiliary toxicity and one patient (12.5%) had grade 3 hepatobiliary toxicity, who was hospitalized for a short-term. The median HPFS was 8.7 months for all patients. The objective response rate was 62%.
Conclusions: A combination of 90Y-RE and gemcitabine at 600 mg/m2 is a safe and potential treatment option for hepatic metastasis of pancreaticobiliary origin.