Phase II study of combination doxorubicin, interferon-alpha, and high-dose tamoxifen treatment for advanced hepatocellular carcinoma.

Abstract

BACKGROUND/AIMS:

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.

METHODOLOGY:

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.

• Authors: Yen-Shen Lu, Chiun Hsu, Chi-Cheng Li, Sung-Hsin Kuo, Kun-Huei Yeh, Chih-Hsin Yang, Chih-Hung Hsu, Chen-Yao Wu, Ann-Lii Cheng
• Journal: Hepato-gastroenterology (Hepatogastroenterology) 2004 May-Jun Vol. 51 Issue 57 Pg. 815-9 ISSN: 0172-6390 [Print] Greece
• PMID: 15143923 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Antineoplastic Agents, Hormonal
• Interferon-alpha
• Tamoxifen
• Doxorubicin

Topics

• Adult
• Antibiotics, Antineoplastic (administration & dosage)
• Antineoplastic Agents, Hormonal (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Disease Progression
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Female
• Humans
• Interferon-alpha (administration & dosage)
• Liver Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Tamoxifen (administration & dosage)