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Dual modulation of 5‐fluorouracil using leucovorin and hydroxyurea. A phase I trial
Author(s) -
Lokich J.,
Anderson N.,
Bern M.,
Coco F.,
Zipoli T.,
Moore C.,
Gonsalves L.
Publication year - 1991
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19910815)68:4<744::aid-cncr2820680414>3.0.co;2-r
Subject(s) - medicine , dose , regimen , fluorouracil , gastroenterology , stomatitis , population , chemotherapy , surgery , environmental health
Oral hydroxyurea (HU) was added to a regimen of 5‐fluorouracil (5‐FU) plus leucovorin (LCV) administered as a continuous 24‐hour infusion for 14 days. A previous report of the 5‐FU plus LCV infusion established optimal dosages of 200 mg/m 2 /d and 5 mg/m 2 /d, respectively, for each agent. Oral HU was added to the regimen in total dosages of 0.5 g/d, 1.0 g/d, 1.5 g/d, or 2.0 g/d. Twenty‐two patients received a total of 45 courses of treatment. Stomatitis was the dose‐limiting side effect; it occurred in 3 of 14 courses with HU at 0.5 g/d (21%) and 9 of 17 courses with HU at 1.0 g/d (53%). Dosage escalation to 1.5 g/d or 2.0 g/d was possible in only 3 of 22 patients (17%). The median time to stomatitis was 10 days (range, 7 to 12 days). One response was observed in this heavily pretreated population. Phase II trials of HU plus LCV dual modulation of infusional 5‐FU should use initial HU dosages of 0.5 g/d for the 14‐day regimen described, with dose escalation as tolerated. Variable oral absorption presumably accounts for the small group of patients who can tolerate the higher doses of HU.