Dual modulation of 5-fluorouracil using leucovorin and hydroxyurea. A phase I trial

✍ Scribed by J. Lokich; N. Anderson; M. Bern; F. Coco; T. Zipoli; C. Moore; L. Gonsalves

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 318 KB
• Volume: 68
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(19910815)68:4<744::aid-cncr2820680414>3.0.co;2-r

✦ Synopsis

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/mz/d and 5 mg/mz/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 1 2 days). One response was observed in this heavily pretreated population. Phase I1 trials of HU plus LCV dual modulation of infusional5-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. Cancer 68: 744-746,1991.