Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma

被引:13
作者
Benson, AB
Mitchell, E
Abramson, N
Klencke, B
Ritch, P
Burnham, JP
McGuirt, C
Bonny, T
Levin, J
Hohneker, J
机构
[1] Northwestern Univ, Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA
[2] Thomas Jefferson Univ, Philadelphia, PA 19107 USA
[3] Baptist Reg Canc Inst, Jacksonville, FL USA
[4] Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA
[5] Med Coll Wisconsin, Milwaukee, WI 53226 USA
[6] Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA
关键词
chemotherapy; dihydropyrimidine dehydrogenase; eniluracil; 5-fluorouracil; inoperable hepatocellular carcinoma;
D O I
10.1093/annonc/mdf079
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Conventional systemic chemotherapy currently available for patients with inoperable hepatocellular carcinoma is ineffective. The purpose of this study was to evaluate the safety and efficacy of eniluracil/5-fluorouracil (5-FU) in the treatment of patients with this highly refractory disease. Patients and methods: This multicenter. open-label study evaluated a 28-day oral regimen of 5-FU (1 mg/m(2) twice daily) plus the dihydropyrimidine dehydrogenase inhibitor, eniluracil (10 mg/m(2) twice daily). in patients with chemotherapy-naive or anthiacycline-refractory inoperable hepatocellular carcinoma. Results: A total of 36 patients enrolled into the study. No patient showed a confirmed partial or complete tumor response, although nine patients (25%) had a best response of stable disease. The median duration of progression-free survival was 9.6 weeks [95% confidence interval (CI) 9.1-10.6 weeks]. and the median duration of overall survival was 32.7 weeks (95% CI 17.4-71.6 weeks). Eniluracil/5-FU was well tolerated. Diarrhea, the most frequent treatment-related non-hematological toxicity. occur-red in 11 patients (31%). Hematological toxicities were infrequent and usually mild. Conclusions: Eniluracil/5-FU as a 28-day oral outpatient regimen is well tolerated by patients with inoperable hepatocellular carcinoma, although minimal activity was observed when given as monotherapy at the dose used in this study.
引用
收藏
页码:576 / 581
页数:6
相关论文
共 28 条
[1]   Eniluracil treatment completely inactivates dihydropyrimidine dehydrogenase in colorectal tumors [J].
Ahmed, FY ;
Johnston, SJ ;
Cassidy, J ;
O'Kelly, T ;
Binnie, N ;
Murray, GI ;
van Gennip, AH ;
Abeling, NGGM ;
Knight, S ;
McLeod, HL .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (08) :2439-2445
[2]   Phase I and pharmacologic study of oral fluorouracil on a chronic daily schedule in combination with the dihydropyrimidine dehydrogenase inactivator eniluracil [J].
Baker, SD ;
Diasio, RB ;
O'Reilly, S ;
Lucas, VS ;
Khor, SP ;
Sartorius, SE ;
Donehower, RC ;
Grochow, LB ;
Spector, T ;
Hohneker, JA ;
Rowinsky, EK .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (04) :915-926
[3]   Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase [J].
Baker, SD ;
Khor, SP ;
Adjei, AA ;
Doucette, M ;
Spector, T ;
Donehower, RC ;
Grochow, LB ;
Sartorius, SE ;
Noe, DA ;
Hohneker, JA ;
Rowinsky, EK .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (12) :3085-3096
[4]   HEPATOCELLULAR-CARCINOMA IN ITALIAN PATIENTS WITH CIRRHOSIS [J].
COLOMBO, M ;
DEFRANCHIS, R ;
DELNINNO, E ;
SANGIOVANNI, A ;
DEFAZIO, C ;
TOMMASINI, M ;
DONATO, MF ;
PIVA, A ;
DICARLO, V ;
DIOGUARDI, N .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (10) :675-680
[5]   DETERMINATION OF NUMBER OF PATIENTS REQUIRED IN A PRELIMINARY AND A FOLLOW-UP TRIAL OF A NEW CHEMOTHERAPEUTIC AGENT [J].
GEHAN, EA .
JOURNAL OF CHRONIC DISEASES, 1961, 13 (04) :346-&
[6]   SOUTHWEST-ONCOLOGY-GROUP STANDARD RESPONSE CRITERIA, END-POINT DEFINITIONS AND TOXICITY CRITERIA [J].
GREEN, S ;
WEISS, GR .
INVESTIGATIONAL NEW DRUGS, 1992, 10 (04) :239-253
[7]   5-FLUOROURACIL BY PROTRACTED VENOUS INFUSION - A REVIEW OF RECENT CLINICAL-STUDIES [J].
HANSEN, RM .
CANCER INVESTIGATION, 1991, 9 (06) :637-642
[8]  
HO DH, 1986, ANTICANCER RES, V6, P781
[9]  
HUAN S, 1989, CANCER, V63, P419, DOI 10.1002/1097-0142(19890201)63:3<419::AID-CNCR2820630303>3.0.CO
[10]  
2-Z