Standard dose (Mayo regimen) 5-fluorouracil and low dose folinic acid: Prohibitive toxicity?

Despite the perception that standard 5-fluorouracil/folinic acid (5-FU/FA) (425 mg/m(2) per day and 20 mg/m(2) per day intravenously once daily x 5 ev ery 4 or 5 weeks) is well tolerated, we have been impressed by toxicity see n and frequent need for dose modification. We performed a retrospective ana lysis to quantitate the proportion of patients experiencing toxicity and at tempted to identify associated clinical characteristics. One hundred thirty -four patients received 5-FU/FA at standard doses described by the Mayo reg imen. Patient characteristics were as follows: female 35%, median age 66 ye ars, Eastern Cooperative Oncology Group performance status less than or equ al to 2, 96%. Sixty-eight percent received chemotherapy for metastatic dise ase. Forty-seven patients (35% +/- 8%) experienced significant toxicity and were unable to receive the second cycle as scheduled: 76% required dose re duction, 11% discontinued therapy (including two toxic deaths), 11% discont inued therapy during the first cycle, and 2% required dose delay. Logistic regression was used to explore the following as predictors of toxicity: age , sex, performance status, adjuvant versus metastatic setting, prior chemot herapy, prior radiation, mean corpuscular volume, red blood cell distributi on width, albumin, alkaline phosphatase, aspartate aminotransferase, biliru bin, and calculated creatinine clearance. No clinical characteristic was fo und to predict toxicity. Only high bilirubin approached statistical signifi cance. We conclude that standard 5-FU/FA, when used in the general populati on, is associated with significant toxicity. Known clinical characteristics are not helpful in predicting toxicity. The lack of previous formal phase I evaluation of this regimen of 5-FU/FA raises concerns regarding its safet y and generalizability in clinical practice.