Phase II study of a weekly 24-hour infusion with 5-fluorouracil and simultaneous sodium-folinic acid in the first-line treatment of metastatic colorectal cancer.
BACKGROUND
A weekly continuous 24-hour infusion therapy with 5-fluorouracil (5-FU) and calcium - folinic acid (CA-FA) was shown to be an effective first-line treatment in advanced metastatic colorectal cancer. Sodium - folinic acid (S-FA) is a new formulation which, in contrast to CA-FA allows the simultaneous i.v. administration in combination with 5-FU in one pump.


METHODS
From 1997 to 1998, 51 patients [median age 60 (range 24-77) years; 38 male, 13 female] with metastatic colorectal cancer were recruited in 5 centers to receive weekly 24-hour infusions of 5-FU (2,600 mg/m(2)) and S-FA (500 mg/m(2)) dissolved in one pump for 6 weeks as first-line treatment. The treatment cycle was repeated after a 2-week rest period.


RESULTS
1,178 administrations (median 24, range 3-54) were performed during the study. Out of 51 patients (median follow-up 20.2 months), 2 (3.9%) achieved complete remission (CR), 17 (33.3%) partial remission (PR), and 21 (41.2%) no change (NC). Progressive disease (PD) was observed in 11/51 (21.6%) patients, including 6 patients who did not complete the first cycle. Median time to tumor progression (TTP) was 8.5 months (95% CI: 5.8-11.3). 32/51 (62.7%) patients survived for more than 1 year, the median survival was reached at 16.5 months (95%CI: 10.2-22.8). Among major toxicities, NCICTC grade III/IV diarrhea occurred in 13/51 (25.4%), grade III hand-foot syndrome in 6/51 (11.7%) patients. Grade III/IV stomatitis was observed in 4/51 (7.8%), cardiac toxicity occurred in 2/51 patients (3.9%).


CONCLUSIONS
Similar to conventional 24-hour 5-FU + CA-FA treatment, the combination with S-FA induced 37.2% objective responses with moderate toxicity. However, TTP seems favorable and the administration of S-FA is convenient, while saving costs and time for the patient in outpatient units.
Hartung
G
G
Onkologisches Zentrum, III. Medizinische Klinik, Universitätsklinikum Mannheim der Universität Heidelberg, Mannheim. Gernot.Hartung@med.uni-rostock.de
Hofheinz
R D
RD
Wein
A
A
Riedel
C
C
Rost
A
A
Fritze
D
D
Kreuser
E D
ED
Drees
M
M
Kühnel
J
J
Hehlmann
R
R
Queisser
W
W
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012964:Sodium / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate
D012964:Sodium; D002955:Leucovorin; D005472:Fluorouracil