Journal of Clinical Oncology, Vol 21, Issue 5
(March), 2003: 807-814
© 2003 American Society for Clinical Oncology
Phase III Comparison of Two Irinotecan Dosing Regimens in Second-Line Therapy of Metastatic Colorectal Cancer
Charles S. Fuchs,
Melvin R. Moore,
Graydon Harker,
Luis Villa,
David Rinaldi,
J. Randolph Hecht
From the Dana-Farber Cancer Institute, Boston, MA; Georgia Cancer Research Center, Decatur, GA; Intermountain Hematology/Oncology Associates, PC, Salt Lake City, UT; Oncology Radiation Associates, PC, Mercy Hospital, Miami, FL; Louisiana Oncology Associates, Lafayette, LA; and UCLA Medical Center, Los Angeles, CA.
Address reprint requests to Charles S. Fuchs, MD, Dana-Farber Cancer Institute, 44 Binney Street, Office Dana 1232, Boston, MA 02115; email: charles_fuchs{at}dfci.harvard.edu.
Purpose: Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients.
Patients and Methods: This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m2) or once every 3 weeks (350 mg/m2, or 300 mg/m2 in patients who were  70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation).
Results: With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P = .42), median survival (9.9 v 9.9 months, respectively; P = .43), or median time to progression (4.0 v 3.0 months, respectively; P = .54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P = .002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P = .35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P = .12). Global quality of life was not statistically different between treatment groups.
Conclusion: Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.
Supported by Pharmacia Corporation, Peapack, NJ.
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