Phase II Study of a Weekly 8-Hour 5-Fluorouracil and Leucovorin Infusion for Patients with Advanced Colorectal Cancer: Dose Adjusted According to its Toxicity
Background: 5-fluorouracil (5-FU) clearly behaves as two different drugs according to the schedules for its administration. A weekly, 8-h 5-FU continuous infusion (CI) regimen may produce a dual effect, because it elicits both a high plasma 5-FU level and also a durable exposure to 5-FU, which may h...
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Published in | Japanese journal of clinical oncology Vol. 31; no. 12; pp. 610 - 615 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
01.12.2001
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | Background: 5-fluorouracil (5-FU) clearly behaves as two different drugs according to the schedules for its administration. A weekly, 8-h 5-FU continuous infusion (CI) regimen may produce a dual effect, because it elicits both a high plasma 5-FU level and also a durable exposure to 5-FU, which may have the advantage of inhibiting both DNA synthesis and RNA activities. The plasma 5-FU level, however, cannot be monitored in most hospitals, so we initiated a pragmatic clinical trial with this weekly 8-h 5-FU CI regimen and adjusted the drug’s dose according to the detected toxicity. Methods: The initial dose of 5-FU was 1200 mg/m2 and this was escalated by 200 mg/m2 weekly, provided that no evidence of significant (grade 2 or greater) toxicity became apparent. Twenty-six patients entered the study from June 1998 to March 1999. Results: The median dose of 5-FU delivered was 1600 mg/m2. The major symptoms precluding dose escalation were nausea and vomiting. Seven patients demonstrated a partial response (26.9%), 11 patients revealed stable disease (42.3%) and eight exhibited progressive disease (30.8%). Conclusion: This weekly 8-h CI 5-FU protocol with the adjustment of dose according to toxicity was not able to achieve the same 5-FU dose and response rate as in previous studies with pharmacokinetic monitoring of 5-FU levels. However, with the concurrent administration of intensive anti-emetic premedication, it is still possible to achieve adequate plasma 5-FU levels by adjusting the 5-FU dose according to elicited toxicity. |
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Bibliography: | istex:8690491EAFE6AFB6FC4A11428F17DFCF0D983749 local:hye131 Received May 9, 2001; accepted September 5, 2001. ark:/67375/HXZ-2JT4ZJHW-M |
ISSN: | 0368-2811 1465-3621 1465-3621 |
DOI: | 10.1093/jjco/hye131 |