Significance of thymidine phosphorylase in metronomic chemotherapy using CPT-11 and doxifluridine for advanced colorectal carcinoma.
BACKGROUND
A phase II study was designed to evaluate the efficacy, safety and predictors for response of metronomic chemotherapy using weekly low-dosage CPT-11 and doxifluridine (5'-DFUR) in 45 patients with metastatic colorectal cancer.


METHODS
Forty mg/m2 of CPT-11 was administered for 3 consecutive weeks in a 4-week treatment cycle, with 5'-DFUR (800 mg/day) given orally.


RESULTS
One or more adverse effects were seen in 42 patients. However, most of these were mild at grade 1 or 2, including only leucopenia in 2, neutropenia in 1, diarrhea in 1 and nausea in 1 as grade 3. The objective response rate was 36% with a median overall survival of 452 days. The response rate in patients with a high expression of thymidine phosphorylase (dThdPase) in tumor cells (47%) was higher (p=0.092) than that (19%) in patients with a low expression.


CONCLUSIONS
The efficacy of metronomic chemotherapy using low-dosage weekly CPT-1 and 5'-DFUR is worthy of further clinical study, especially in patients with a high expression of dThdPase in primary tumor cells.
Ogata
Yutaka
Y
Department of Surgery, Kurume University School of Medicine, Kurume, 830-0011, Japan. yogata@med.kurume-u.ac.jp
Sasatomi
Teruo
T
Mori
Shinjiro
S
Matono
Keiko
K
Ishibashi
Nobuya
N
Akagi
Yoshito
Y
Fukushima
Takanaru
T
Murakami
Hidetsugu
H
Ushijima
Masataka
M
Shirouzu
Kazuo
K
D015720:5'-Nucleotidase / Q000096:biosynthesis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011355:Prodrugs / Q000008:administration & dosage; D011446:Prospective Studies
D011355:Prodrugs; D005467:Floxuridine; D000077146:Irinotecan; D015720:5'-Nucleotidase; C025034:doxifluridine; D002166:Camptothecin