Chemoradiation of hepatic malignancies: Prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization

Purpose Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 (⁹⁰Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of ⁹⁰Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. Methods and Materials Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver ⁹⁰Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after ⁹⁰Y infusion. If a DLT was not observed, the ⁹⁰Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of ⁹⁰Y with full-dose capecitabine. Results Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing ⁹⁰Y MTD were not met, indicating an MTD of >170 Gy. Conclusion The MTD of ⁹⁰Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest ⁹⁰Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.