Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer

Background: This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. Methods: Patients with advanced unresectable liver-dom...

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Bibliographic Details
Published in:	British journal of cancer Vol. 111; no. 2; pp. 265 - 271
Main Authors:	Cohen, S J, Konski, A A, Putnam, S, Ball, D S, Meyer, J E, Yu, J Q, Astsaturov, I, Marlow, C, Dickens, A, Cade, D N, Meropol, N J
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 15-07-2014 Nature Publishing Group
Subjects:	631/154/109/1940 692/699/1503/1607 692/699/67/1059/485 692/699/67/1059/99 Aged Aged, 80 and over Antimetabolites, Antineoplastic - administration & dosage Antimetabolites, Antineoplastic - adverse effects Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cancer therapies Capecitabine Chemotherapy Clinical Study Cohort Studies Colorectal cancer Deoxycytidine - administration & dosage Deoxycytidine - adverse effects Deoxycytidine - analogs & derivatives Dosimetry Drug Resistance Embolization, Therapeutic - methods Epidemiology Female Fluorouracil - administration & dosage Fluorouracil - adverse effects Fluorouracil - analogs & derivatives Humans Liver Male Maximum Tolerated Dose Medical sciences Metastasis Microspheres Middle Aged Molecular Medicine Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasms - drug therapy Neoplasms - radiotherapy Neoplasms - therapy Oncology Patients Prospective Studies Radiation therapy Toxicity Tumors Yttrium Radioisotopes - administration & dosage Yttrium Radioisotopes - adverse effects United States > US Pennsylvania radioembolization capecitabine phase I Antineoplastic agent Human Microsphere Capecitabine Fluoropyrimidine derivatives Prodrug Malignant tumor Cancerology Treatment Phase I trial Advanced stage Resins Yttrium Pyrimidine nucleoside Cancer
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Summary:	Background: This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. Methods: Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375–1000 mg/m 2 b.i.d.) for 14 days every 21 days. Radioembolization with 90 Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine. Results: Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m 2 . The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively. Conclusions: This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m 2 b.i.d. is recommended for phase II study with sequential lobar radioembolization.
ISSN:	0007-0920 1532-1827
DOI:	10.1038/bjc.2014.344