Phase II study of UFT with leucovorin plus hepatic arterial infusion with irinotecan, 5-fluorouracil and leucovorin for non-resectable liver metastases of colorectal cancer.
BACKGROUND
Compared with systemic therapy, hepatic arterial infusion (HAI) increases the response to fluoropyrimidines.


METHODS
Thirty-one patients with non-resectable, colorectal cancer (CRC) liver metastases received irinotecan 120 mg/m(2), followed by leucovorin (LV) 20 mg/m(2) and 5-fluorouracil (5-FU) 500 mg/m(2) administered by HAI every 2 weeks, plus UFT (tegafur-uracil) 200 mg/m(2)/day with LV 30 mg/day on days 1-22, followed by a 6-day rest.


RESULTS
The objective response rate was 65% (all 20 patients achieving a partial response). Ten patients (32%) had stable disease. The median time to progression (TTP) and overall survival (OS) were 12 and 36 months. OS was similar in patients with low versus high expression of thymidylate synthase (TS) and/or dihydropyrimidine dehydrogenase (DPD). The regimen was well tolerated.


CONCLUSIONS
UFT with LV plus HAI irinotecan and 5-FU/LV was a feasible and effective treatment for non-resectable CRC liver metastases, increasing response, TTP and OS. TS and DPD levels in liver metastases did not predict outcome.
Idelevich
Efraim
E
Institute of Oncology, Kaplan Medical Center, Rehovot, Israel. efraim_i@clalit.org.il
Greif
Franklin
F
Mavor
Eli
E
Miller
Rafael
R
Kashtan
Hanoch
H
Susmalian
Sergo
S
Ariche
Arie
A
Brenner
Baruch
B
Baruch
Noa Ben
NB
Dinerman
Michael
M
Shani
Adi
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000473:pathology*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
D005641:Tegafur; D014498:Uracil; D000077146:Irinotecan; D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin