Continuous infusion fluorouracil/leucovorin and bolus mitomycin-C as a salvage regimen for patients with advanced colorectal cancer.
BACKGROUND
No effective systemic salvage therapy exists for patients with advanced colorectal cancer who progress after receiving bolus fluorouracil (FU) and leucovorin (LV) chemotherapy. In vitro data suggest that bolus FU resistance can be overcome by continuous infusion (CI) FU, and that the cytotoxic effects of Mitomycin-C (MMC) and FU are synergistic. Based on this data, a Phase II trial of CI FU and LV with bolus MMC in patients with advanced colorectal carcinoma who progressed on only one previous chemotherapy regimen was performed.


METHODS
Twenty-eight patients with advanced colorectal carcinoma who had progressed after one previous chemotherapy regimen of bolus FU/LV were treated with bolus MMC 10 mg/m2 every 6 weeks and CI FU 200 mg/m2/day admixed with LV 10 mg/m2/day given 14 days on/7 days off.


RESULTS
The partial response rate in 24 evaluable patients was 17% (95% confidence interval, 2-32%) with a median response duration of 9.5 months (range, 4.2-12.0 months). Twelve (50%) additional patients achieved disease stabilization. Median survival was 9.9 months in the whole group (28 patients) and 11.5 months in the 24 evaluable patients. The major toxicities were grade 4 diarrhea occurring in two patients and grade 3 mucositis occurring in five patients. There was minimal myelosuppression (grade 3 thrombocytopenia in one patient) and no occurrences of hand-foot syndrome or cardiotoxicity.


CONCLUSIONS
This regimen demonstrates modest activity with acceptable toxicity in colorectal cancer patients who have failed a single-bolus FU/LV regimen. Modifications of this and other infusional FU-based chemotherapy regimens should be explored as potential salvage chemotherapy regimens in advanced colorectal cancer.
Conti
J A
JA
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, New York 10021.
Kemeny
N E
NE
Saltz
L B
LB
André
A M
AM
Grossano
D D
DD
Bertino
J R
JR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009061:Mouth Mucosa; D012074:Remission Induction; D016879:Salvage Therapy; D013280:Stomatitis / Q000139:chemically induced; D015996:Survival Rate
D016685:Mitomycin; D002955:Leucovorin; D005472:Fluorouracil