Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy.
OBJECTIVE
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.


METHODS
Twenty-five irinotecan-naive 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.


CONCLUSIONS
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.
van Hazel
Guy A
GA
Perth Radiologic Clinic, Mount Medical Centre, Perth, Western Australia, Australia.
Pavlakis
Nick
N
Goldstein
David
D
Olver
Ian N
IN
Tapner
Michael J
MJ
Price
David
D
Bower
Geoffrey D
GD
Briggs
Gregory M
GM
Rossleigh
Monica A
MA
Taylor
D James
DJ
George
Jacob
J
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001315:Australia; D001918:Brachytherapy; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000556:secondary*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008863:Microspheres; D008875:Middle Aged; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome; D015020:Yttrium Isotopes / Q000008:administration & dosage* / Q000009:adverse effects
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D019275:Radiopharmaceuticals; D059004:Topoisomerase I Inhibitors; D015020:Yttrium Isotopes; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin