A 3-day schedule of 5-fluorouracil and folinic acid in metastatic progressive colorectal cancer and its impact in terms of palliation.
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.
Schöber
C
C
Department of Hematology/Oncology, Medical School of Hannover, Germany.
Köhne-Wömpner
C H
CH
Schmoll
H J
HJ
Stahl
M
M
Wilke
H J
HJ
Poliwoda
H
H
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
D002955:Leucovorin; D005472:Fluorouracil