• A L Cheng, K H Yeh, R L Fine, S E Chuang, C H Yang, L H Wang, and D S Chen.
• Department of Internal Medicine, National Taiwan University Hospital, Taipei.
• Hepato Gastroenterol. 1998 Nov 1; 45 (24): 1955-60.

Background/AimsIn vitro data have indicated that tamoxifen (> 2.5 uM) significantly enhances the cytotoxic effect of doxorubicin in hepatocellular carcinoma (HCC) cells. This clinical study was conducted to examine whether tamoxifen, at a dose sufficient to result in a plasma concentration of more than 2.5 uM, may improve the therapeutic efficacy of doxorubicin in patients with advanced HCC.MethodologyA prospective phase II study was conducted. Eligible patients had unresectable and non-embolizable HCC, objectively measurable tumors, adequate neogram with absolute granulocyte count > 2,000/mm3 and platelet count > 1 x 10/mm3, total serum bilirubin < 3.0 mg/dl, age > or = 75 year, and a Karnofsky performance status < or = 50%. The treatment included oral tamoxifen 40 mg/m2, q.i.d, Day 1 to 7, and intravenous doxorubicin 60 mg/m2, Day 4, repeated every 3 weeks.ResultsBetween May 1994 and December 1996, a total of 38 patients were enrolled in the study. Thirty-six patients were evaluable for tumor response and treatment-related toxicities. There were 32 men and 4 women, with a median age of 49 years. They received an average of 3.8 (range:1-12) courses of chemotherapy. ECOG (Eastern Cooperative Oncology Group) Grade 3-4 leucopenia and Grade 3-4 thrombocytopenia developed in 27.2% and 12.5% courses given, respectively. Gastrointestinal toxicity was generally mild. Three patients developed symptomatic cardiac toxicity. Twelve patients (33.3%, 95% confidence interval 17-51%) had achieved a partial remission (PR), with a median progression-free survival of 7 months. Median survivals of the responders and non-responders were 10 and 3 months, respectively (p<0.05). The median Karnofsky performance status of the responders improved from 74.0+/-6.3% to a post-chemotherapy value of 93.2+/-4.6% (p<0.05)ConclusionsHigh dose tamoxifen appears to be an effective biochemical modulator of doxorubicin in the treatment of HCC. Prospective randomized phase III studies comparing doxorubicin alone versus doxorubicin plus high-dose tamoxifen are needed.

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