Dose-escalating study of yttrium 90 microspheres with capecitabine for intrahepatic cholangiocarcinoma or metastatic disease to the liver.

Abstract

TPS216 Background: Radiosensitizing chemotherapy has been shown to improve outcomes compared to radiation alone for several gastrointestinal cancers. Delivery of internal radiation to primary and metastatic hepatic malignancies provides an opportunity to enhance radiation effects when used with radiosensitizing chemotherapy. Y90, integrated into nonbiodegradable microspheres, is a brachytherapy treatment option that can be administered by intra-arterial hepatic injection, delivering high radiation doses to tumors while sparing liver parenchyma that results in tumoricidal effects with minimal liver toxicity. Capecitabine is an oral, tumor-activated fluoropyrimidine that preferentially delivers 5-FU to tumor cells via thymidine phosphorylase (TP). As TP is up-regulated by radiotherapy, internal tumor radiation may increase preferential delivery of 5-FU to the tumor. This study will identify the maximally tolerated dose (MTD) of Y90 that can be administered with standard dose of capecitabine for the treatment of intrahepatic cholangiocarcinoma and/or intrahepatic liver metastases, characterize the toxicity of capecitabine and Y90, and determine time to tumor progression. Methods: Eligible patients have histologically confirmed intrahepatic cholangiocarcinoma or metastatic cancer confined to the liver that represents <50% of total liver volume. No more than two prior therapies for hepatic metastatic disease, no prior hepatic radiation and no prior intervention or compromise of the Ampulla of Vater are permitted. The proposed sample size ranges from 12 to 20 patients. Subjects will be treated with sequential cycles of capecitabine for 14 days of a 21-day cycle and receive an assigned dose of Y90 between days 1 and 7 of cycle two. Dose-limiting toxicity (DLT) will be determined up to 6 weeks from Y90 infusion. The primary endpoint will be to determine the maximum tolerated dose of Y90 with capecitabine. Secondary endpoints will include evaluation of overall and hepatic response. Hepatic response will be measured with cross-sectional imaging. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MDS Nordion