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

Autor: David Goldstein, Guy van Hazel, David H. Price, Monica A. Rossleigh, Nick Pavlakis, Michael Tapner, Ian N. Olver, Gregory M. Briggs, Geoffrey D. Bower, D. James Taylor, Jacob George
Přispěvatelé: van Hazel, Guy A, Pavlakis, Nick, Goldstein, David, Olver, Ian N, Tapner, Michael J, Price, David, Bower, Geoffrey D, Briggs, Gregory M, Rossleigh, Monica A, Taylor, D James, George, Jacob
Rok vydání: 2009
Předmět:
Male
Cancer Research
Time Factors
Colorectal cancer
medicine.medical_treatment
Brachytherapy
Gastroenterology
Enzyme Inhibitors
Infusions
Intravenous
irinotecan
Liver Neoplasms
Middle Aged
Microspheres
Treatment Outcome
Oncology
Chemotherapy
Adjuvant
Fluorouracil
Female
Colorectal Neoplasms
medicine.drug
Adult
Antimetabolites
Antineoplastic
medicine.medical_specialty
Maximum Tolerated Dose
medicine.drug_class
colorectal cancer
Irinotecan
Antimetabolite
Disease-Free Survival
Drug Administration Schedule
Internal medicine
Yttrium Isotopes
medicine
Humans
Aged
Chemotherapy
business.industry
Australia
Cancer
medicine.disease
Surgery
fluorouracil chemotherapy
Radiation therapy
Drug Resistance
Neoplasm
Concomitant
randomized controlled trial
Camptothecin
Radiotherapy
Adjuvant
Radiopharmaceuticals
Topoisomerase I Inhibitors
business
liver metastases
Zdroj: Journal of Clinical Oncology. 27:4089-4095
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2008.20.8116
Popis: 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.
Databáze: OpenAIRE
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