Chemoradiation of Hepatic Malignancies: Prospective, Phase 1 Study of Full-Dose Capecitabine With Escalating Doses of Yttrium-90 Radioembolization

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• 作者：Ryan Hickey ; MD^&lowast ; ; Mary F. Mulcahy ; MD^&dagger ; ; Robert J. Lewandowski ; MD^&lowast ; ; Vanessa L. Gates ; MS^&lowast ; ; Michael Vouche ; MD^&lowast ; ; Ali Habib ; BA^&lowast ; ; Sheetal Kircher ; MD^&dagger ; ; Steven Newman ; MD^&dagger ; ; Halla Nimeiri ; MD^&dagger ; ; Al B. Benson ; MD^&dagger ; ; Riad Salem ; MD^&lowast ; ; ^&dagger ; ; ^{r-salem@northwestern.edu" class="auth_mail}
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：1 April, 2014
• 年：2014
• 卷：88
• 期：5
• 页码：1025-1031
• 全文大小：349 K

文摘

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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聽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聽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聽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聽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.