Background. Prolonged infusional 5‐fluorouracil (5‐FU) and bolus 5‐FU modulated by leucovorin are associated with higher response rates than bolus 5‐FU alone. Cisplatin enhances 5‐FU cytotoxicity in some preclinical models. Methods. The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5‐FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer. Results. Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5‐FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar‐plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA‐directed toxicity of 5‐FU. The median tolerated dose level of 5‐FU was 113 mg/m2/d (range, 64–150 mg/m2/d). Mean steadystate plasma concentrations (Cpss) of 5‐FU appeared to increase linearly from 0.19 μM to 0.39 μM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5‐FU Cpss than patients with grade 0 or 1 toxicity. Conclusions. The early onset of toxicity with this regimen of protracted infusional 5‐FU/high‐dose leucovorin and weekly cisplatin required marked attenuation of the 5‐FU dose intensity, and the results were no better than that expected with infusional 5‐FU alone.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Aug 1 1993|
- biochemical modulation
- colorectal cancer
ASJC Scopus subject areas
- Cancer Research