Phase II study of combination doxorubicin, interferon-alpha, and high-dose tamoxifen treatment for advanced hepatocellular carcinoma.
OBJECTIVE
Our previous studies showed that high-dose tamoxifen may improve the therapeutic efficacy of doxorubicin (HTD regimen) in hepatocellular carcinoma. Interferon-alpha, either as a single-agent treatment or as a biochemical modulator, has also been reported to be effective in the treatment of hepatocellular carcinoma. In this study, we sought to clarify if the addition of Interferon-alpha2b to HTD regimen could further improve the control of advanced hepatocellular carcinoma.


METHODS
Eligible patients had unresectable and non-embolizable hepatocellular carcinoma, objectively measurable tumors, adequate hemogram and major organ function, age > or = 75 year, and a Karnofsky performance status > or = 60%. The treatment included oral tamoxifen 40 mg/m2, q.i.d., Day 1-7; interferon-alpha2b subcutaneous injection, 5 MU/m2, q.d. (Day 3-5) and 3 MU/m2, q.o.d. (Day 6-21); and intravenous doxorubicin 60 mg/m2, Day 4, repeated every 4 weeks.


RESULTS
From May 1997 through July 2002, a total of 30 patients were enrolled, 25 of whom were eligible for assessment of response and toxicity. These included 20 men and 5 women, with a median age of 45 years. They received an average of 3.5 (range: 1-8) courses of chemotherapy. Grade 3-4 leukopenia and Grade 3-4 thrombocytopenia developed in 46.7% and 51.0% of treatment courses, respectively. Gastrointestinal toxicity was generally mild. One patient achieved a complete remission and remained disease-free at this report, with a progression-free survival of 49 months at last follow-up in September 2002. Five patients achieved a partial remission, with a median progression-free survival of 7 months. The total response rate was 24% (95% confidence interval 9.4-45.1%). Median survival for all 25 patients was 6.0 months and the 1-year survival rate was 16%.


CONCLUSIONS
Combination of interferon-alpha2b, high-dose tamoxifen, and doxorubicin is an effective treatment for advanced hepatocellular carcinoma. However, the data does not support that addition of interferon-alpha2b is superior to HTD regimen alone.
Lu
Yen-Shen
YS
Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Hsu
Chiun
C
Li
Chi-Cheng
CC
Kuo
Sung-Hsin
SH
Yeh
Kun-Huei
KH
Yang
Chih-Hsin
CH
Hsu
Chih-Hung
CH
Wu
Chen-Yao
CY
Cheng
Ann-Lii
AL
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013629:Tamoxifen / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D016898:Interferon-alpha; D013629:Tamoxifen; D004317:Doxorubicin