Combination therapy of oral fluoropyrimidine anticancer drug S-1 and interferon alpha for HCC patients with extrahepatic metastases.
OBJECTIVE
There is no standard treatment for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. We assessed the efficiency and safety of the oral fluoropyrimidine anticancer drug S-1 combined with interferon alpha (IFN-alpha) for HCC patients with extrahepatic metastases.


METHODS
Twenty-nine HCC patients with extrahepatic metastases received S-1/IFN. One cycle of combination therapy represented 2 weeks followed by 2-4 weeks of rest. In each cycle, S-1 was administrated orally at 80-120 mg (depending on body surface area) every day and IFN-alpha intramuscularly at 5 million units thrice weekly.


RESULTS
The overall response of 29 patients was complete response (CR) in 4 (14%), partial response (PR) in 1, stable disease in 4, progressive disease in 12, and dropout in 8 patients. Objective response (CR + PR) was 17%. The time to progression and survival rate were significantly higher in patients with lung metastases (n = 19) than in those with painful bone metastases (n = 7; p = 0.0058 and 0.0015). With regard to NCI-CTC grade 3 adverse reactions, 3 (10%), 3 (10%) and 2 (7%) patients developed anorexia, leukopenia, and neutropenia, respectively. No grade 4 adverse reaction or toxicity-related death occurred.


CONCLUSIONS
S-1/IFN is a potentially safe and suitable combination therapy for HCC patients with extrahepatic metastases, especially those with lung metastases.
Uka
Kiminori
K
Programs for Biomedical Research, Division of Frontier Medical Science, Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Aikata
Hiroshi
H
Mori
Nami
N
Takaki
Shintaro
S
Kawakami
Yoshiiku
Y
Azakami
Takahiro
T
Kawaoka
Tomokazu
T
Jeong
Soo Cheol
SC
Takahashi
Shoichi
S
Chayama
Kazuaki
K
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D012074:Remission Induction; D012189:Retrospective Studies; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
D004338:Drug Combinations; D016898:Interferon-alpha; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid