A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma.

Abstract

We determined the therapeutic effect of fluorouracil (5-FU) in combination with folinic acid (FA) in patients with measurable recurrent or metastatic carcinoma of the colon or rectum by comparing it to standard 5-FU therapy in a prospective randomized controlled trial. Patients were randomized to receive either FA, 200 mg/m2/d for five consecutive days, or nothing. All patients received 5-FU, 370 mg/m2/d for five days on the first course, with subsequent dose modifications to maintain equal toxicity in the two arms. One hundred thirty patients were entered on trial and only five were excluded from the analysis because they did not meet the eligibility criteria or they refused therapy after randomization. The two treatment arms were balanced for 11 clinical characteristics. Patients were evaluated for response at the end of every two treatment courses and toxicity after every course of therapy. Median follow-up was 1.45 years. Dose-limiting toxicity was mucositis and diarrhea on this treatment schedule, although neutropenia was apparent. The response rate was 33% (21 of 63 patients) in the 5-FU and FA arm and was 7% (four of 61 patients) in the 5-FU arm (P less than .0005). Time to disease progression was significantly different in the combination arm as compared with the single-agent arm (P = .023). Overall survival was significantly longer for patients treated with 5-FU and FA as compared with those receiving 5-FU alone (P = .05). The median survival was 12.6 months for patients receiving the combination, and 9.6 months for those receiving 5-FU alone. Our results indicate that the combination of 5-FU and FA is effective treatment for patients with metastatic or recurrent carcinoma of the rectum and colon who have not received prior chemotherapy.

The effect of 5-fluorouracil and alpha interferon and 5-fluorouracil and leucovorin on cellular anti-tumour immune responses in patients with advanced colorectal cancer

“…It is known to augment natural killer (NK) cell activity, and it up-regulates expression of both class I MHC antigen and tumour-associated antigen in tumours (Trincheri et al, 1985) (Erlichman et al, 1988). There were no differences between the study and control groups in terms of age, sex, burden or distribution of disease or performance status.…”

“…The mean ages were 58 (range 27-76) for the control group and 60 (42-78) for those receiving 5-FU with IFN-a. All patients had histologically proven metastatic colorectal cancer, the sites of metastases being shown in Table I (Erlichman et al, 1988). There were no differences between the study and control groups in terms of age, sex, burden or distribution of disease or performance status.…”

Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer

“…The response to this drug varies depending on whether bolus or infusional chemotherapy is given. (Erlichman et al, 1988;Advanced Colorectal Cancer Meta-Analysis Project, 1992) During the last decade it has become clear that biomodulation with folinic acid (FA) and alteration of the scheduling of 5-FU can significantly improve the response rate and toxicity profile (de Gramont et al, 1997). Nevertheless, only about 20 -30% of patients respond to 5-FU based therapy (Skibber et al, 2001) and patients with metastatic disease are not cured by chemotherapy.…”

A phase II study of epidoxorubicin in colorectal cancer and the use of cyclosporin-A in an attempt to reverse multidrug resistance

“…Despite the very intensive research for more effective agents for the treatment of colorectal cancer, 5-fluorouracil (5-FU) remains the most effective with a response rate of 5-15% (Moertel, 1978;Chlebowski et al, 1980;Ehrlichman et al, 1988;Doroshow et al, 1990). A more recent approach with the addition of leucovorin to 5-FU indeed yields a higher response rate, but this is achieved at the cost of increased toxicity and without a meaningful survival benefit (Ehrlichman et Doroshow et al, 1990).…”