Weekly fluorouracil and high-dose leucovorin: efficacy and treatment of cutaneous toxicity
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Intensive therapy with 5-fluorouracil (FU) and leucovorin (LV) has proved to be effective in the treatment of advanced colorectal cancer. The toxicity of this regimen has not been systematically evaluated. In the present study, 52 patients with advanced colorectal and refractory cancers received sequential 2-month cycles of weekly FU and high-dose LV and were monitored for toxicity as well as response in 103 cycles. Of 24 evaluable patients with colorectal cancer, 1 complete and 9 partial responses were seen (42%); 4 of 10 patients who had been refractory to conventional FU treatment responded to the FU/LV regimen. One partial response was observed among six patients with gastric carcinoma, and three minor responses were seen in five women with refractory breast cancer. A total of 24 patients (46%) completed the first cycle on schedule, although 7 subjects required a reduction in the dose of FU. The majority of patients required treatment breaks because of toxicity. Gastrointestinal toxicity proved to be dose-limiting on this schedule, necessitating FU dose modification and treatment of both diarrhea in 15 subjects and acute abdominal pain in 7 cases. No patient required a further treatment delay of FU dose adjustment. Myelosuppression was an uncommon complication on this regimen. Cutaneous toxicity was also prominent in this series of patients, with the hand-foot syndrome developing in 14 cases (27%); 11 subjects who developed this complication were treated with pyridoxine (150 mg daily), and all experienced improvement in their symptoms within 1 week. Partial and complete responses were observed in 41% of evaluable patients with colorectal cancer and in one of six evaluable patients with gastric carcinoma. We conclude that FU and high-dose LV can safely be given on a weekly basis, although acute gastrointestinal and cutaneous toxicity are common.
KeywordsClin Oncol Leucovorin Princess Margaret Hospital Cutaneous Toxicity Leucovorin Calcium
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