A randomized trial comparing defined-duration with continuous irinotecan until disease progression in fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer.
OBJECTIVE
Irinotecan given until disease progression is an accepted standard treatment for advanced colorectal cancer (CRC) resistant to fluoropyrimidines. It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control. We performed a multicenter phase III trial to compare the two policies of defined-duration versus continuous irinotecan treatment.


METHODS
Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered. After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks, 55 patients with responding or stable disease were randomly assigned to stop irinotecan (n = 30) or continue until disease progression (n = 25). Registered patients were not randomly assigned predominantly due to disease progression (n = 236) and intolerable toxicity (n = 38).


RESULTS
From the time of random assignment, there were no differences in failure-free survival (P = .999) or overall survival (P = .11) between the two arms. No difference was seen in mean global health status quality-of-life score between the two arms at 12 weeks after random assignment. No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after random assignment.


CONCLUSIONS
For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.
Department of Medicine, Royal Marsden Hospital, Downs Rd, Sutton, Surrey, United Kingdom SM2 5PT.
Rohit
R
Lal
James
J
Dickson
David
D
Cunningham
Ian
I
Chau
Andrew R
AR
Norman
Paul J
PJ
Ross
Clare
C
Topham
Gary
G
Middleton
Mark
M
Hill
Jacqui
J
Oates
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D000077146:Irinotecan; D013940:Thymidylate Synthase; D002166:Camptothecin