Journal article
A phase II and pharmacokinetic study of 6S-leucovorin plus 5-fluorouracil in patients with colorectal carcinoma
Investigational new drugs, Vol.13(2), pp.149-155
1995
DOI: 10.1007/BF00872864
PMID: 8617578
Abstract
Leucovorin (LV) is commonly used as a modulator of 5-fluorouracil (5-FU) cytotoxicity. In patients with colon cancer, the addition of LV to 5-FU improves response rates, and in some trials has improved survival in advanced disease and in the adjuvant setting. Leucovorin is generally administered as a racemic mixture, but the isomers differ substantially in pharmacokinetics and biological activity, with 6S-LV the predominant active component. The current study was undertaken to determine the effect of 6R on the pharmacokinetics of 6S-LV, and to characterize the toxicity and antitumor effect of 5-FU when administered with 6S-LV to patients with advanced colorectal carcinoma. Thirty patients were treated with weekly 5-FU plus high dose 6S-LV. To determine the effects of 6R-LV on the pharmacokinetics of 6S-LV, 20 patients were randomly assigned to receive either 250 mg/m2 6S-LV or 500 mg/m2 6R,S-LV as a 2 hour IV infusion on day -2, and the other preparation on day -1, with pharmacokinetics measured each day. The presence of 6R-LV had no effect on the AUC, Clp, Cmax, or terminal phase t1/2 of 6S-LV. The overall response rate was 40% (C.I. 23-60%). The most frequent toxicities were gastrointestinal. In this small cohort, scheduled and delivered dose intensity was positively associated with response (p=0.05). These results show that there is no pharmacokinetic advantage to the use of 6S-LV rather than 6R,S-LV as a modulator of 5-FU. © 1995 Kluwer Academic Publishers.
Details
- Title: Subtitle
- A phase II and pharmacokinetic study of 6S-leucovorin plus 5-fluorouracil in patients with colorectal carcinoma
- Creators
- Neal J. Meropol - Roswell Park Cancer InstituteNicholas J. Petrelli - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer InstituteMiguel Rodriguez-Bigas - Surgical OncologyLeslie E. Blumenson - Roswell Park Cancer InstituteCheryl Frank - Roswell Park Cancer InstituteElmer Berghorn - Roswell Park Cancer InstitutePatrick J. Creaven - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Investigational new drugs, Vol.13(2), pp.149-155
- DOI
- 10.1007/BF00872864
- PMID
- 8617578
- ISSN
- 0167-6997
- eISSN
- 1573-0646
- Language
- English
- Date published
- 1995
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359843802771
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