Schedule-selective biochemical modulation of 5-fluorouracil: a phase II study in advanced colorectal cancer.

摘要: Based on experimental findings suggesting that 5-fluorouracil (FUra) may have different mechanisms of action depending the schedule administration, we generated hypothesis biochemical modulation this fluoropyrimidine should be specific. We thus tested activity a hybrid regimen consisting two biweekly cycles FUra bolus (600 mg/m2) modulated by pretreatment (24-h interval) with methotrexate (200 mg/m2), alternating 3-week continuous infusion mg/m2/day) low-dose (6S)leucovorin (20 mg/m2 weekly). Thirty-three consecutive patients advanced measurable colorectal cancer and no prior therapy for metastatic disease entered study from February 1992 to August 1993. They were treated preceded The median Eastern Cooperative Oncology Group performance status was 1; liver only site in 17 patients. Treatment outcome evaluated computed tomographic scan all patients, except two. Three complete 13 partial responses obtained among these 33 (response rate, 48%; 95% confidence limits, 31-66%). Performance (Eastern Group) influenced clinical response. combined response rate 69%, 33%, 25% an 0, 1, 2, respectively (chi2, 4.6, P = 0.032, two-tailed Mantel test trend). After follow-up time 26 months, 10 are still alive. progression-free survival overall 9.5 20.2 respectively. No toxic deaths or grade 4 toxicity occurred. incidence 3 per patient any cycle was: mucositis 6%, diarrhea 3%, vomiting 3% part 21%, respectively, regimen. Hand-foot syndrome occurred 27%