Fluorodeoxyuridine with continuous leucovorin infusion. A phase II clinical trial in patients with metastatic colorectal cancer.
BACKGROUND
Chemotherapy of colon cancer has used the modulation of 5-fluorouracil (5-FU) by leucovorin; however, early studies indicate that leucovorin with fluorodeoxyuridine (FUDR) may be clinically superior. The authors report their experience in patients with metastatic colorectal cancer.


METHODS
One hundred twelve evaluable patients with metastatic colorectal cancer were treated with leucovorin and FUDR. Leucovorin was given by continuous intravenous infusion at 500 mg/m2/day on days 1-6, and FUDR was given by intravenous push on days 2-6 at 3:00 p.m. daily, with doses ranging from 270-1350 mg/m2/day.


RESULTS
This regimen was well tolerated with dose-limiting toxicity of diarrhea and stomatitis, while hematologic toxicity was minimal. At least one chemotherapy regimen had previously failed in 90 of 112 patients (80%). Twenty major responses greater than or equal to partial remission, lasting from 2-40+ months, were observed in this patient population for an overall response rate of 18%. Twelve of 22 previously untreated patients (55%) had major responses. Overall survival of previously untreated patients was 73% (14 of 19) and 50% (11 of 22) at 1 and 2 years, respectively. Of 66 patients who had received prior leucovorin-5-FU (LVFU) therapy with subsequent disease progression, 4 had major responses lasting 95, 241, 350, and 432 days, respectively.


CONCLUSIONS
These data suggest that the modulation of FUDR by leucovorin may have clinical use. The recommended starting dose of FUDR is 800 mg/m2/day on days 2-6, with subsequent escalation each month in those patients who do not display stomatitis.
Levin
R D
RD
Cancer Treatment Centers of America & Midwestern Regional Medical Center, Zion, Illinois.
Gordon
J H
JH
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004359:Drug Therapy, Combination; D005260:Female; D005467:Floxuridine / 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; D009362:Neoplasm Metastasis; D012074:Remission Induction; D013280:Stomatitis / Q000139:chemically induced; D015996:Survival Rate
D005467:Floxuridine; D002955:Leucovorin