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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

2009; Lippincott Williams & Wilkins; Volume: 27; Issue: 25 Linguagem: Inglês

10.1200/jco.2008.20.8116

1527-7755

Guy A. Van Hazel, Nick Pavlakis, David Goldstein, Ian Olver, Michael Tapner, David Price, Geoffrey D. Bower, Gregory M. Briggs, Monica A. Rossleigh, DianeE. Taylor, George Casella,

Cholangiocarcinoma and Gallbladder Cancer Studies

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/m 2 on days 1 and 8 of a 3-week cycle for the first two cycles, and full irinotecan doses (ie, 100 mg/m 2 ) 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/m 2 (obstructive jaundice, thrombocytopenia, diarrhea), in five of 13 patients at 75 mg/m 2 (neutropenia, leukopenia, thrombocytopenia, elevated alkaline phosphatase, abdominal pain, ascites, fatigue) and in four of six patients at 100 mg/m 2 (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/m 2 on days 1 and 8 of a 3-week cycle.