Journal of Clinical Oncology, Vol 16, 3461-3475, Copyright © 1998 by American Society of Clinical Oncology
Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer
A Sulkes, SE Benner and RM Canetta
Department of Clinical Oncology, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Wallingford, CT, USA. asolkes@ccsg.tau.ac.il
PURPOSE AND DESIGN:This review describes the early clinical development of
uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding
uracil to ftorafur. The review focuses on the treatment of colorectal
cancer and summarizes the Japanese experience and the phase I and II trials
performed in the United States and Europe. RESULTS: Clinical trials of UFT
published in the Western world have included 581 patients with colorectal
cancer. UFT has been administered in these trials as a single agent or
biomodulated by leucovorin (LV). UFT was administered daily in split doses
for periods that ranged from 14 to 28 days. The activity of oral UFT in
large-bowel cancer when administered with oral LV (approximately 50
mg/dose) has resulted in objective response rates of approximately 40%.
Response rates of approximately 25% (range, 17% to 39%) were reported when
UFT was administered as a single agent or with lower doses of LV. The
highest dose-intensities of UFT are achieved with 28-day schedules of
administration. The maximum- tolerated dose (MTD) of UFT with this
schedule, when administered concomitantly with oral LV 150 mg daily, is 300
mg/m2 daily. The dose- limiting toxicity (DLT) of UFT has generally been
diarrhea. Other commonly described toxicities include nausea and vomiting,
fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically,
hand-foot syndrome and neurologic toxicity are lacking. CONCLUSION: UFT is
a fluoropyrimidine active in colorectal cancer. The oral route of
administration and improved safety profile represent important advantages
over both conventional and infusional fluorouracil (5-FU) regimens.
This article has been cited by other articles:
|
|
|
|
 
B. M. Wolpin, J. A. Meyerhardt, H. J. Mamon, and R. J. Mayer
Adjuvant Treatment of Colorectal Cancer
CA Cancer J Clin,
May 1, 2007;
57(3):
168 - 185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Meyerhardt and R. J. Mayer
Systemic Therapy for Colorectal Cancer
N. Engl. J. Med.,
February 3, 2005;
352(5):
476 - 487.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Ichikawa, H. Uetake, Y. Shirota, H. Yamada, N. Nishi, Z. Nihei, K. Sugihara, and R. Hirayama
Combination of Dihydropyrimidine Dehydrogenase and Thymidylate Synthase Gene Expressions in Primary Tumors as Predictive Parameters for the Efficacy of Fluoropyrimidine-based Chemotherapy for Metastatic Colorectal Cancer
Clin. Cancer Res.,
February 1, 2003;
9(2):
786 - 791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Mayer
Oral Versus Intravenous Fluoropyrimidines for Advanced Colorectal Cancer: By Either Route, It's All the Same
J. Clin. Oncol.,
November 1, 2001;
19(21):
4093 - 4096.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-K. Lin, W.-S. Wang, R.-K. Hsieh, T.-C. Hsu, T.-J. Chiou, J.-H. Liu, F. S. Fan, C.-C. Yen, T.-C. Lin, J.-K. Jiang, et al.
Phase II Study of Oral Tegafur-Uracil and Folinic Acid as First-line Therapy for Metastatic Colorectal Cancer: Taiwan Experience
Jpn. J. Clin. Oncol.,
November 1, 2000;
30(11):
510 - 514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R.B. Arbuckle, S.L. Huber, and C. Zacker
The Consequences of Diarrhea Occurring During Chemotherapy for Colorectal Cancer: A Retrospective Study
Oncologist,
June 1, 2000;
5(3):
250 - 259.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Y. Fujiwara
Current Status of Oral Anticancer Drugs in Japan
J. Clin. Oncol.,
October 1, 1999;
17(10):
3362 - 3365.
[Full Text]
[PDF]
|
|
|
|
