title: Chemoradiation of hepatic malignancies: prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization.
abstract: OBJECTIVE
  Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ((90)Y) 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 (90)Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver.
  
  
  METHODS
  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 (90)Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after (90)Y infusion. If a DLT was not observed, the (90)Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of (90)Y 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 (90)Y MTD were not met, indicating an MTD of >170 Gy.
  
  
  CONCLUSIONS
  The MTD of (90)Y 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 (90)Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.
authors.forename: Ryan
authors.initials: R
authors.lastname: Hickey
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Mulcahy
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lewandowski
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Gates
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.
authors.forename: Michael
authors.initials: M
authors.lastname: Vouche
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.
authors.forename: Ali
authors.initials: A
authors.lastname: Habib
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Kircher
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Steven
authors.initials: S
authors.lastname: Newman
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Halla
authors.initials: H
authors.lastname: Nimeiri
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois; Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois. Electronic address: r-salem@northwestern.edu.
authors.forename: Riad
authors.initials: R
authors.lastname: Salem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000379:methods*; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000532:radiotherapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011874:Radiometry / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome; D015019:Yttrium / Q000627:therapeutic use*
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D015019:Yttrium; D000069287:Capecitabine; D005472:Fluorouracil