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Radioembolization of Liver Metastases From Colorectal Cancer Using Yttrium-90 Microspheres With Concomitant Systemic Oxaliplatin, Fluorouracil, and Leucovorin Chemotherapy

Ricky A. Sharma, Guy A. Van Hazel, Bruno Morgan, David P. Berry, Keith Blanshard, David Price, Geoffrey Bower, Jennifer A. Shannon, Peter Gibbs, William P. Steward

From the Department of Radiation Oncology and Biology, University of Oxford, Churchill Hospital, Oxford; Departments of Oncology, Radiology, and Surgery, University Hospitals of Leicester, Leicester, UK; Perth Oncology, Mount Medical Centre, Perth, NSW; Medical Oncology, Nepean Hospital, Sydney; and the Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Australia

Address reprint requests to Ricky Sharma, MD, PhD, Radiation Oncology and Biology, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK; e-mail: ricky.sharma{at}rob.ox.ac.uk

Purpose Liver metastases represent the principal cause of death in patients with advanced colorectal cancer (CRC). Injection of resin microspheres (SIR Spheres)—containing the ß-emitter, yttrium-90—into the arterial supply of the liver can cause radioembolization of metastases. This treatment has not been tested with the radiosensitizing chemotherapy, oxaliplatin, which appears synergistic in the treatment of CRC when combined with fluorouracil and leucovorin (FOLFOX).

Patients and Methods A phase I study of SIR-Spheres therapy with modified FOLFOX4 systemic chemotherapy was conducted in patients with inoperable liver metastases from CRC who had not previously received chemotherapy for metastatic disease. Oxaliplatin (30 to 85 mg/m²) was administered for the first three cycles with full FOLFOX4 doses from cycle 4 until cycle 12. The primary end point was toxicity.

Results Twenty patients were enrolled onto the study. Five patients experienced National Cancer Institute (NCI; Bethesda, MD) grade 3 abdominal pain, two of whom had microsphere-induced gastric ulcers. The dose-limiting toxicity was grade 3 or 4 neutropenia, which was recorded in 12 patients. One episode of transient grade 3 hepatotoxicity was recorded. Mean splenic volume increased by 92% following 6 months of protocol therapy. Partial responses were demonstrated in 18 patients and stable disease in two patients. Two patients underwent partial hepatic resection following protocol therapy. Median progression-free survival was 9.3 months, and median time to progression in the liver was 12.3 months.

Conclusion The maximum-tolerated dose was 60 mg/m² of oxaliplatin for the first three cycles, with full FOLFOX4 doses thereafter. This chemoradiation regime merits evaluation in phase II-III trials.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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