Dr. Goldberg has received research support, payment for expert testimony, and speaker's honoraria from Pharmacia (now Pfizer [New York, NY]) and Sanofi-Synthelabo (Paris, France).
Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin
Results from Intergroup Trial N9741
Article first published online: 6 OCT 2004
Copyright © 2004 American Cancer Society
Volume 101, Issue 10, pages 2170–2176, 15 November 2004
How to Cite
Delaunoit, T., Goldberg, R. M., Sargent, D. J., Morton, R. F., Fuchs, C. S., Findlay, B. P., Thomas, S. P., Salim, M., Schaefer, P. L., Stella, P. J., Green, E. and Mailliard, J. A. (2004), Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin. Cancer, 101: 2170–2176. doi: 10.1002/cncr.20594
- Issue published online: 29 OCT 2004
- Article first published online: 6 OCT 2004
- Manuscript Revised: 14 JUL 2004
- Manuscript Accepted: 14 JUL 2004
- Manuscript Received: 1 MAR 2004
- Pharmacia (now Pfizer [New York, NY])
- Sanofi-Synthelabo (Paris, France)
- colorectal carcinoma;
- gastrointestinal toxicity;
- treatment-related mortality
Intergroup Trial N9741 evaluated 5-fluorouracil (5-FU)/leucovorin (LV) administered in conjunction with either irinotecan or oxaliplatin in the first-line treatment of advanced colorectal carcinoma (CRC). The current report describes two treatment arms that were withdrawn from the protocol due to unexpected treatment-related toxicities and a high mortality rate. The complications observed in these arms highlight the importance of aggressive and immediate supportive care in the management of digestive toxicity.
In Trial N9741, patients were randomly assigned to receive one of the following six regimens: 1) irinotecan plus bolus 5-FU/LV (Arm A); 2) sequential irinotecan plus bolus 5-FU/LV (Arm B); 3) bolus 5-FU/LV only (Mayo Clinic regimen; Arm D); 4) oxaliplatin plus bolus 5-FU/LV (Arm E); 5) oxaliplatin plus infusional 5-FU/LV (Arm F); or 6) oxaliplatin plus irinotecan (Arm G). In the current study, the authors investigated treatment-related toxicity in patients who received either of the two combination regimens containing daily bolus 5-FU (i.e., patients in Arm B or Arm E).
Sixty-one and 47 patients were enrolled in Arm B and Arm E, respectively. Diarrhea and neutropenia were the most common toxicities in both groups. Five patients in Arm B (8.2%) and 4 patients in Arm E (8.5%) died within 60 days of study entry. All fatal toxicities occurred within 15 days of treatment administration, and all deaths were associated with the simultaneous occurrence of multiple symptoms, which were dominated by Grade ≥ 3 diarrhea.
Combination regimens containing daily bolus 5-FU/LV and oxaliplatin or irinotecan can be associated with severe gastrointestinal toxicity and high mortality rates. Therefore, the authors recommend the use of more tolerable infusional 5-FU–based regimens in the treatment of metastatic CRC. Cancer 2004. © 2004 American Cancer Society.