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

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

International journal of radiation oncology, biology, physics (2014-03-26)
Ryan Hickey, Mary F Mulcahy, Robert J Lewandowski, Vanessa L Gates, Michael Vouche, Ali Habib, Sheetal Kircher, Steven Newman, Halla Nimeiri, Al B Benson, Riad Salem
摘要

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. 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. 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. 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.

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Sigma-Aldrich
2'-脱氧胞苷, ≥99% (HPLC)
Sigma-Aldrich
卡培他滨, ≥98% (HPLC)
Sigma-Aldrich
钇, powder, −40 mesh, 99.5% trace rare earth metals basis
Sigma-Aldrich
钇, chips, 99.9% trace rare earth metals basis
卡培他滨, European Pharmacopoeia (EP) Reference Standard
钇, foil, not light tested, 25x25mm, thickness 0.005mm, as rolled, 99%
钇, rod, 100mm, diameter 6.35mm, cast, 99%
钇, rod, 50mm, diameter 12.5mm, cast, 99%
钇, rod, 50mm, diameter 2.0mm, cast, 99%
钇, rod, 50mm, diameter 6.35mm, cast, 99%
钇, wire reel, 0.05m, diameter 0.5mm, 99.9%
钇, wire reel, 0.05m, diameter 1.0mm, 99.9%
钇, wire reel, 0.05m, diameter 1.0mm, square section, 99.9%
钇, wire reel, 0.1m, diameter 0.5mm, 99.9%
钇, wire reel, 0.1m, diameter 1.0mm, 99.9%
钇, wire reel, 0.2m, diameter 0.5mm, 99.9%
钇, wire reel, 0.2m, diameter 1.0mm, 99.9%
钇, foil, 25x25mm, thickness 0.125mm, as rolled, 99%
钇, foil, 25x25mm, thickness 0.15mm, as rolled, 99%
钇, foil, 50x50mm, thickness 0.125mm, as rolled, 99%
钇, foil, 50x50mm, thickness 0.15mm, as rolled, 99%
钇, foil, 25mm disks, thickness 0.50mm, as rolled, 99%
钇, foil, not light tested, 100x100mm, thickness 0.025mm, as rolled, 99%
钇, foil, not light tested, 25x25mm, thickness 0.025mm, as rolled, 99%
钇, foil, not light tested, 50x50mm, thickness 0.025mm, as rolled, 99%
钇, rod, 100mm, diameter 12.5mm, cast, 99%
Sigma-Aldrich
钇, diam. × thickness 2.00 in. × 0.25 in., 99.9% trace metals basis
Sigma-Aldrich
钇, ingot, 99.9% trace rare earth metals basis