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

Ryan M Hickey, Mary Frances Mulcahy, Robert J Lewandowski, Vanessa L. Gates, Michael Vouche, Ali Habib, Sheetal Mehta Kircher, Steven Newman, Halla S Nimeiri, Al B Benson III, Riad Salem*

*Corresponding author for this work

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23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1025-1031
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume88
Issue number5
DOIs
StatePublished - Apr 1 2014

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Yttrium
yttrium
Maximum Tolerated Dose
dosage
Liver
Neoplasms
liver
Cholangiocarcinoma
toxicity
Radiation-Sensitizing Agents
Capecitabine
Gastrointestinal Neoplasms
Radiation Effects
Radiotherapy
cycles
Radiation
metastasis
Neoplasm Metastasis
radiation
chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

@article{fef3de4ff5af4ece91ce476a4c1dd555,
title = "Chemoradiation of hepatic malignancies: Prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization",
abstract = "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.",
author = "Hickey, {Ryan M} and Mulcahy, {Mary Frances} and Lewandowski, {Robert J} and Gates, {Vanessa L.} and Michael Vouche and Ali Habib and Kircher, {Sheetal Mehta} and Steven Newman and Nimeiri, {Halla S} and {Benson III}, {Al B} and Riad Salem",
year = "2014",
month = "4",
day = "1",
doi = "10.1016/j.ijrobp.2013.12.040",
language = "English (US)",
volume = "88",
pages = "1025--1031",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
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}

TY - JOUR

T1 - Chemoradiation of hepatic malignancies

T2 - Prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization

AU - Hickey, Ryan M

AU - Mulcahy, Mary Frances

AU - Lewandowski, Robert J

AU - Gates, Vanessa L.

AU - Vouche, Michael

AU - Habib, Ali

AU - Kircher, Sheetal Mehta

AU - Newman, Steven

AU - Nimeiri, Halla S

AU - Benson III, Al B

AU - Salem, Riad

PY - 2014/4/1

Y1 - 2014/4/1

N2 - 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.

AB - 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.

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