Modified Irinotecan/5FU/Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes.
OBJECTIVE
To evaluate the efficacy and safety of a regimen using Irinotecan, 5FU and Leucovorin for patients with advanced or recurrent colorectal cancer.


METHODS
Irinotecan (75 mg/m(2)) was administered biweekly, while 5FU (600 mg/m(2)) and Leucovorin (250 mg/m(2)) were administered weekly, for 6 weeks.


RESULTS
The 21 consecutive patients subjected to this regimen showed a good response rate (43%) with minimal toxicity (incidence of grade 3/4: leukopenia and neutropenia, 5%, respectively, and vomiting, 10%). The mean survival time of all 21 patients was 15.7 months. This regimen could be a valid option for patients with advanced colorectal cancer, especially those seeking a good QoL (quality of life) for the remainder of their lives. We evaluated the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) mRNAs, and sialyl Lewis X on formalin-fixed, paraffin-embedded colorectal tumor samples. Expression of TS mRNA or sialyl Lewis X was negatively correlated with the response from chemotherapy. Patients with low DPD mRNA expression in the tumor showed a significant longer survival than those with high expression. In patients with high TP mRNA expression, there was a tendency towards a high incidence of leukopenia.


CONCLUSIONS
Some predictive factors elucidated in this study could contribute to the progress of the tumor-biology based, individualized chemotherapy for colorectal cancer patients.
Yanagisawa
Yoko
Y
Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Maruta
Fukuto
F
Iinuma
Nobuyoshi
N
Ishizone
Satoshi
S
Koide
Naohiko
N
Nakayama
Jun
J
Miyagawa
Shinichi
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000401:mortality; D000328:Adult; D000368:Aged; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000401:mortality; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D016256:Lewis X Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000032:analysis; D009962:Orotate Phosphoribosyltransferase / Q000032:analysis; D011379:Prognosis; D000080506:Sialyl Lewis X Antigen; D015996:Survival Rate; D013939:Thymidine Phosphorylase / Q000378:metabolism; D013940:Thymidylate Synthase / Q000378:metabolism; D014803:Vitamin B Complex / Q000008:administration & dosage
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D016256:Lewis X Antigen; D009844:Oligosaccharides; C056315:ST 439 antigen, human; D000080506:Sialyl Lewis X Antigen; D014803:Vitamin B Complex; D000077146:Irinotecan; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin