title: A 3-day schedule of 5-fluorouracil and folinic acid in metastatic progressive colorectal cancer and its impact in terms of palliation.
abstract: Treatment results in advanced colorectal cancer have improved during the last decade since the incorporation of agents like folinic acid, PALA, or interferon as active biomodulation of 5-fluorouracil (5-FU), the most potent drug in this disease. But essential prolongation of survival could not be demonstrated. To better define the need to initiate therapy and duration of treatment, a phase II study of high-dose folinic acid and 5-FU was initiated in patients with documented progression or severe tumor-related symptoms prior to start of therapy until best response was observed. The treatment plan was folinic acid 300 mg/m2 as a 10-minute intravenous infusion followed 50 minutes later by 5-FU 600 mg/m2 intravenous bolus days 1 to 3 every 3 to 4 weeks. Thirty-seven consecutive patients were treated during November 1986 and October 1987. Because of severe tumor-related symptoms, immediate treatment was considered mandatory in only eight patients. In the remaining 29 primarily asymptomatic patients, an observational period of a median duration of 8 weeks (range, 1-56) was possible before treatment seemed to be indicated. Most patients experienced some toxicity, mostly leukopenia and gastrointestinal side effects, of World Health Organization grades 3 and 4 during 156 treatment cycles (range, one to eight cycles). The calculated dose intensity was 535 mg/m2 5-FU per week. Of 36 evaluable patients, 14 responded at least with a partial remission (39%; confidence interval, 23% to 55%) of 7 months median duration. An additional 13 patients (36%) had stable disease, giving a rate of tumor stabilization in these progressive patients of 75%, for a median duration of 5.5 months. Median survival since start of therapy was 11 months. Results are comparable to data reported in the literature; survival and remission duration seem not to be mitigated in a patient population in which therapy was withheld until progression or symptoms occur. This patient population might be characterized by more homogeneously distributed risk factors.
authors.affiliation: Department of Hematology/Oncology, Medical School of Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schöber
authors.forename: C H
authors.initials: CH
authors.lastname: Köhne-Wömpner
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: M
authors.initials: M
authors.lastname: Stahl
authors.forename: H J
authors.initials: HJ
authors.lastname: Wilke
authors.forename: H
authors.initials: H
authors.lastname: Poliwoda
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged
chemical_list: D002955:Leucovorin; D005472:Fluorouracil