WEEKLY THERAPY WITH FOLINIC ACID (FA) AND HIGH-DOSE 5-FLUOROURACIL (5-FU) 24-HOUR INFUSION IN PRETREATED PATIENTS WITH METASTATIC COLORECTAL-CARCINOMA - A MULTICENTER STUDY BY THE ASSOCIATION OF MEDICAL ONCOLOGY OF THE GERMAN-CANCER-SOCIETY (AIO)

Background: No effective salvage therapy is known for patients with metastatic colorectal carcinoma progressive after chemotherapy with-fluorouracil (5-FU)/folinic acid (FA) or 5-FU/alpha interferon (IFN) combinations. The aim of the study was to test whether weekly FA/high-dose 5-FU is an effective therapy in pretreated patients with progressive metastatic colorectal carcinoma. Patients and methods: Between January and December 1992, 57 patients with metastatic colorectal carcinoma were treated with weekly infusions of high-dose 5-fluorouracil (5-FU) (2600 mg/m2 as 24-hour infusion) and folinic acid (FA) (500 mg/m2 as 1-hour infusion prior to 5-FU). All patients were pretreated with chemotherapy, most of them with regimens containing 5-FU i.v. bolus/FA or 5-FU/alfa interferon (IFN), and all had documented progressive disease at the time of entering the study. In patients with partial remission (PR) or stable disease (SD) with improvement of their clinical condition, therapy was continued until progressive disease (PD) was documented. In all other patients therapy was stopped after one course (6 infusions). Results: 5/57 patients (9%) achieved PR, 32/57 (56%) SD, in 19/57 (33%) disease was progressive and one toxic death occured. 26/32 patients (81%) with SD or PR after the first chemotherapy again obtained SD or PR on high-dose 5-FU/FA but only 8/18 (44%) of those with PD after first chemotherapy did so. The median duration of SD/PR was 3 months and the median survival for all patients 8 months (range 3-17+). Apart from one toxic death, toxicity consisting for the most part of mucositis (n = 24), nausea (n = 23), diarrhoea (n = 18) and hand-foot syndrome (n = 12) was moderate. Conclusion: Pretreated patients with metastatic colorectal carcinoma, notably those with a primary PR or SD, can probably benefit from weekly high-dose 5-FU/FA.