Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study.
BACKGROUND
5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate--leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer.


METHODS
Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate--30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV--500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil--600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression.


RESULTS
The median age was 64 yrs (34-84) and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting.


CONCLUSIONS
This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress and may prove encouraging.
Tomlinson
Shannon K
SK
Dept of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. stomlins@wfubmc.edu
Melin
Susan A
SA
Higgs
Vetta
V
White
Douglas R
DR
Savage
Paul
P
Case
Douglas
D
Blackstock
A William
AW
D000008:Abdominal Neoplasms / Q000188:drug therapy / Q000556:secondary; 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* / Q000473:pathology*; D004333:Drug Administration Routes; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000378:metabolism; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate