Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC.


METHODS
All 53 patients received epirubicin (50 mg/m2 i.v.) on day 1 and cisplatin (60 mg/m2 i.v.) after epirubicin administration. Oral UFT 400-600 mg/day, determined by body surface area, and leucovorin 75 mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval.


RESULTS
Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0-26.8%) with median response duration of 17.1 weeks (95% CI; 5.0-29.3 weeks, range; 7.1-51.7 weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6 weeks (95% CI; 17.3-31.9 weeks, range; 3.0-131.3 weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%).


CONCLUSIONS
The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC.
Kim
Seok Jin
SJ
Division of Hematology/Oncology Department of Internal Medicine, Korea University Medical Center, 126-1, Anam-dong 5-ga, Sungbuk-ku, Seoul, 136-705, Korea.
Seo
Hee Yun
HY
Choi
Jong Gwon
JG
Sul
Hye Ryoung
HR
Sung
Hwa Jung
HJ
Park
Kyong Hwa
KH
Choi
In Keun
IK
Oh
Sang Cheul
SC
Yoon
So Young
SY
Seo
Jae Hong
JH
Choi
Chul Won
CW
Kim
Byung Soo
BS
Shin
Sang Won
SW
Kim
Yeul Hong
YH
Kim
Jun Suk
JS
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000931:Antidotes / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006402:Hematologic Diseases / Q000097:blood / Q000139:chemically induced; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D000931:Antidotes; D000970:Antineoplastic Agents; D005641:Tegafur; D015251:Epirubicin; D014498:Uracil; D002945:Cisplatin; D002955:Leucovorin