A PHASE-I TRIAL OF A MODIFIED, DOSE-INTENSIVE FAMTX REGIMEN (HIGH-DOSE 5-FLUOROURACIL PLUS DOXORUBICIN PLUS HIGH-DOSE METHOTREXATE PLUS LEUCOVORIN) WITH ORAL URIDINE RESCUE

Citation
Gk. Schwartz et al., A PHASE-I TRIAL OF A MODIFIED, DOSE-INTENSIVE FAMTX REGIMEN (HIGH-DOSE 5-FLUOROURACIL PLUS DOXORUBICIN PLUS HIGH-DOSE METHOTREXATE PLUS LEUCOVORIN) WITH ORAL URIDINE RESCUE, Cancer, 78(9), 1996, pp. 1988-1995
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CancerACNP
ISSN journal
0008-543X
Volume
78
Issue
9
Year of publication
1996
Pages
1988 - 1995
Database
ISI
SICI code
0008-543X(1996)78:9<1988:APTOAM>2.0.ZU;2-8
Abstract
BACKGROUND. Dose intensification of 5-fluorouracil (5-FU) is complicat ed by increased toxicity. 5-FU is a fluorine-substituted pyrimidine an alog of uracil. In preclinical studies, administration of oral uridine (Ur) has been shown to allow for dose intensification of 5-FU with en hancement of its antitumor activity. Therefore, a Phase I trial was de signed aimed at dose intensification of 5-FU as a component of a modif ied 5-FU-doxorubicin-methotrexate (FAMTX) regimen using oral Ur rescue . METHODS. Methotrexate (MTX) was administered to all patients at a fi xed dose of 1.5 g/m(2). MTX was followed 24 hours later by escalating doses of 5-FU starting at 800 mg/m(2) with leucovorin rescue. Cycles o f 5-FU and MTX were repeated every 15 days. Every other cycle, patient s received doxorubicin (''Adria cycles'') at a dose of 30 mg/m(2). Ora l Ur was administered at a dose of 8 gm/m(2) every 6 hours for 12 dose s. In the first phase of the study, patients received Ur only if they developed Grade 3 or 4 hematologic toxicity. In the second phase, all patients received Ur 24 hours after 5-FU on all cycles. RESULTS. Witho ut Ur rescue, the maximum tolerated dose (MTD) of 5-FU was 900 mg/m(2) on the Adria cycles and 1.1 gm/m(2) on the non-Adria cycles. With Ur, the MTD of 5-FU increased to 1.2 gm/m(2) on the Adria cycles and to 1 .6 gm/m(2) on the non-Adria cycles. CONCLUSIONS. In this modified FAMT X regimen, oral Ur administration allowed for dose-intensification of 5-FU, with a 33% increase in the MTD of 5-FU on the Adria cycles and a 45% increase in the MTD of 5-FU dose on the non-Adria cycles. (C) 199 6 American Cancer Society.