Originally published as JCO Early Release 10.1200/JCO.2008.20.8116 on August 3 2009

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Treatment of Fluorouracil-Refractory Patients With Liver Metastases From Colorectal Cancer by Using Yttrium-90 Resin Microspheres Plus Concomitant Systemic Irinotecan Chemotherapy

From Perth Oncology; Mount Nuclear Medicine; and Perth Radiologic Clinic, Mount Medical Centre, Perth, Western Australia; Departments of Medical Oncology and Radiology, Royal North Shore Hospital, St Leonards; Departments of Oncology and Nuclear Medicine, Prince of Wales Hospital, Randwick; Storr Liver Unit, Westmead Millennium Institute, Westmead; Sirtex Technology Pty, Lane Cove, Sydney, New South Wales; and Departments of Medical Oncology and Radiology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Corresponding author: Michael Tapner, BAppSc, Sirtex Medical, Unit 6, Parkview, Lane Cove Business Park, 16 Mars Rd, Lane Cove, New South Wales 2066, Australia; e-mail: mtapner{at}sirtex.com.

Purpose Liver metastases are the principal cause of death in patients with advanced colorectal cancer (CRC). Irinotecan is a chemotherapeutic agent used in the treatment of CRC and has demonstrated synergistic potential when used with radiation. Radioembolization with yttrium-90 microspheres has demonstrated increased response and survival rates when given with fluorouracil chemotherapy. This study's goal was to evaluate the maximum-tolerated dose of concomitant irinotecan and radioembolization in fluorouracil-refractory patients with CRC hepatic metastases.

Patients and Methods Twenty-five irinotecan-naïve patients who had experienced relapse after previous chemotherapy were enrolled onto three dose-escalating groups. Irinotecan was administered at 50, 75, or 100 mg/m² on days 1 and 8 of a 3-week cycle for the first two cycles, and full irinotecan doses (ie, 100 mg/m²) were administered during cycles 3 to 9. Radioembolization was administered during the first chemotherapy cycle.

Results Most patients experienced acute, self-limiting abdominal pain and nausea. Mild lethargy and anorexia were common. Grades 3 to 4 events were seen in three of six patients at 50 mg/m² (obstructive jaundice, thrombocytopenia, diarrhea), in five of 13 patients at 75 mg/m² (neutropenia, leukopenia, thrombocytopenia, elevated alkaline phosphatase, abdominal pain, ascites, fatigue) and in four of six patients at 100 mg/m² (diarrhea, deep vein thrombosis, constipation, leukopenia). Eleven (48%) of 23 patients had a partial response, and nine patients (39%) had stable disease. The median progression-free survival was 6.0 months; the median survival was 12.2 months.

Conclusion Concomitant use of radioembolization plus irinotecan did not reach a maximum-tolerated dose. The recommended dose of irinotecan in this setting is 100 mg/m² on days 1 and 8 of a 3-week cycle.

Supported by Sirtex Medical, Sydney, Australia; Pfizer, New York, NY; and Pharmacia, Sydney, Australia.

Presented in part at the 31st Annual Meeting of the Clinical Oncology Society of Australia, November 24-26, 2004, ACT, Australia; the American Society of Clinical Oncology GI Symposium, January 27-29, 2005, Hollywood, FL; and the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.

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

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: ACTRN12606000009516.

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