1. Phase I prospective trial of TAS-102 (trifluridine and tipiracil) and radioembolization with 90 Y resin microspheres for chemo-refractory colorectal liver metastases.
- Author
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Fidelman N, Atreya CE, Griffith M, Milloy MA, Carnevale J, Cinar P, Venook AP, and Van Loon K
- Subjects
- Adult, Male, Humans, Female, Middle Aged, Microspheres, Prospective Studies, Uracil adverse effects, Trifluridine adverse effects, Drug Combinations, Antineoplastic Combined Chemotherapy Protocols adverse effects, Colorectal Neoplasms, Liver Neoplasms drug therapy, Liver Neoplasms radiotherapy
- Abstract
Background: Extrahepatic disease progression limits clinical efficacy of Yttrium-90 (
90 Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Trifluridine and tipiracil (TAS-102) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer., Methods: Sequential lobar TARE using90 Y resin microspheres in combination with TAS-102 in 28-day cycles were used to treat adult patients with bilobar liver-dominant chemo-refractory mCRC according to 3 + 3 dose escalation design with a 12-patient dose expansion cohort. Study objectives were to establish safety and determine maximum tolerated dose (MTD) of TAS-102 in combination with TARE., Results: A total of 21 patients (14 women, 7 men) with median age of 60 years were enrolled. No dose limiting toxicities were observed. Treatment related severe adverse events included cytopenias (10 patients, 48%) and radioembolization-induced liver disease (2 patients, 10%). Disease control rate in the liver lobes treated with TARE was 100%. Best observed radiographic responses were partial response for 4 patients (19%) and stable disease for 12 patients (57%)., Conclusions: The combination of TAS-102 and TARE for patients with liver-dominant mCRC is safe and consistently achieves disease control within the liver., Trial Registration: ClinicalTrials.gov identifier NCT02602327 (first posted 11/11/2015)., (© 2022. The Author(s).)- Published
- 2022
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