A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma
Article first published online: 28 JUN 2006
Copyright © 1993 American Cancer Society
Volume 72, Issue 3, pages 663–668, 1 August 1993
How to Cite
Grem, J. L., McAtee, N., Balis, F., Murphy, R., Venzon, D., Kramer, B., Goldspiel, B., Begley, M. and Allegra, C. J. (1993), A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma. Cancer, 72: 663–668. doi: 10.1002/1097-0142(19930801)72:3<663::AID-CNCR2820720307>3.0.CO;2-V
- Issue published online: 28 JUN 2006
- Article first published online: 28 JUN 2006
- Manuscript Accepted: 15 MAR 1993
- colorectal cancer;
- biochemical modulation;
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.