多柔比星、α干扰素和大剂量他莫昔芬联合治疗晚期肝细胞癌的II期研究

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

作者信息

Lu Yen-Shen, Hsu Chiun, Li Chi-Cheng, Kuo Sung-Hsin, Yeh Kun-Huei, Yang Chih-Hsin, Hsu Chih-Hung, Wu Chen-Yao, Cheng Ann-Lii

机构信息

Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Hepatogastroenterology. 2004 May-Jun;51(57):815-9.

PMID:15143923

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.

摘要

背景/目的：我们之前的研究表明，高剂量他莫昔芬可能会提高阿霉素（HTD方案）治疗肝细胞癌的疗效。据报道，α干扰素无论是作为单一药物治疗还是作为生化调节剂，在肝细胞癌治疗中均有效。在本研究中，我们试图阐明在HTD方案中添加α2b干扰素是否能进一步改善晚期肝细胞癌的控制情况。

方法

符合条件的患者患有无法切除且不可栓塞的肝细胞癌、可客观测量的肿瘤、血常规和主要器官功能正常、年龄≥75岁以及卡氏评分≥60%。治疗方案包括口服他莫昔芬40mg/m²，每日4次，第1 - 7天；皮下注射α2b干扰素，5MU/m²，每日1次（第3 - 5天），3MU/m²，隔日1次（第6 - 21天）；静脉注射阿霉素60mg/m²，第4天，每4周重复一次。

结果

从1997年5月至2002年7月，共纳入30例患者，其中25例符合疗效和毒性评估条件。包括20名男性和5名女性，中位年龄45岁。他们平均接受了3.5（范围：1 - 8）个疗程的化疗。3 - 4级白细胞减少和3 - 4级血小板减少分别出现在46.7%和51.0%的疗程中。胃肠道毒性一般较轻。1例患者达到完全缓解，至本报告时仍无疾病进展，在2002年9月最后一次随访时无进展生存期为49个月。5例患者达到部分缓解，中位无进展生存期为7个月。总缓解率为24%（95%置信区间9.4 - 45.1%）。所有25例患者的中位生存期为6.0个月，1年生存率为16%。