Efficacy of high-dose oral leucovorin and 5-fluorouracil in advanced colorectal carcinoma. Plasma and tissue pharmacokinetics.

Thirty-one evaluable patients with advanced colorectal cancer were treated with oral leucovorin (LV) 500 mg/m2, administered hourly in four divided doses weekly for 6 weeks. Six patients received intravenous 5-FU at 450 mg/m2 and the remainder at 600 mg/m2 weekly for 6 weeks. This schedule was repeated after a 2-week rest period without medication. None of the patients had received previous chemotherapy. The results of the study showed a overall complete remission (CR) and partial remission (PR) of 45%. All responding patients received the 600-mg/m2 dose of 5-FU. There were five CR and nine PR. An additional seven (23%) patients had stable disease. Two of the seven received the 450-mg/m2 dose of 5-FU and the remainder received 600 mg/m2. The median disease-free interval for CR patients exceeded 25 months, while the interval for PR patients was 11.8 months. The median survival for CR patients was over 26.7 months and 16.5 months for the PR patients. The median survival for stable patients was 9.5 months and 5.5 months for patients with progressive disease. Toxicity included diarrhea in 70% of patients, excess lacrimal secretion in 35%, and nausea and vomiting in 25% There were no treatment-related deaths in this group. The authors conclude from this Phase I study that the optimal 5-FU dose in 600 mg/m2 combined with high-dose oral leucovorin for the treatment of advanced colorectal carcinoma.