Chronic thalidomide and chemoembolization for hepatocellular carcinoma.
Chronic thalidomide and chemoembolization for hepatocellular carcinoma.
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DOI：
10.1634/theoncologist.2014-0283
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发表时间：
2014-12
期刊：
影响因子：
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通讯作者：
Jennifer Wu;J. Ng;P. Christos;A. Goldenberg;J. Sparano;M. Sung;H. Hochster;F. Muggia
中科院分区：
文献类型：
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作者：
Jennifer Wu;J. Ng;P. Christos;A. Goldenberg;J. Sparano;M. Sung;H. Hochster;F. Muggia
背景：肝细胞癌（HCC）中，经导管动脉化疗栓塞（TACE）已被用于缩短肿瘤血管并延缓肿瘤进展。我们进行了一项I期临床试验，以评估沙利度胺联合TACE治疗晚期HCC患者的疗效和毒性。方法2000年6月至2003年11月，56例不能切除的肝癌患者接受了TACE治疗。沙利度胺的起始剂量为200 mg/天，每2周递增一次，直至耐受的最大剂量为1，000 mg/天。根据毒性确定剂量降低和停药。在开始沙利度胺治疗后4周进行TACE，必要时重复。结果：总体而言，47例和55例患者的反应和毒性，分别进行评估，沙利度胺的中位剂量为200毫克/天。3例患者（6.38%）达到完全缓解，10例（21.3%）部分缓解，总缓解率为27.7%，27例（57.5%）病情稳定。中位无进展生存期为7个月（95%置信区间[CI]：5-10个月），中位OS为21个月（95% CI：16-28个月）（图1）。疲劳和嗜睡（49.1%），便秘（47.3%）和恶心（43.6%）是常见的。3-4级毒性主要包括天冬氨酸转氨酶升高（43.6%）和丙氨酸转氨酶升高（38.2%）（表1）。结论沙利度胺和TACE的非血液学副作用较常见，以疲乏和便秘为主。由于缺乏明确的治疗获益，这种联合治疗不太可能用于HCC。
BACKGROUND Transcatheter arterial chemoembolization (TACE) has been used to curtail tumor vasculature and delay tumor progression in hepatocellular carcinoma (HCC). We conducted a phase I trial to evaluate the efficacy and toxicity of thalidomide when combined with TACE in patients with advanced HCC. METHODS Between June 2000 and November 2003, 56 patients with unresectable HCC and amenable to TACE were enrolled. The starting dose of thalidomide was 200 mg/day and was escalated every 2 weeks as tolerated to a maximum dose of 1,000 mg/day. Dose reductions and discontinuation were determined by toxicity. TACE was performed 4 weeks after initiation of thalidomide therapy and repeated as necessary. RESULTS Overall, 47 and 55 patients were evaluable for response and toxicity, respectively; the median dose of thalidomide given was 200 mg/day. Three patients (6.38%) patients achieved complete responses, whereas 10 (21.3%) had partial responses, for an overall response rate of 27.7%, and 27 (57.5%) had stable disease. Median progression-free survival was 7 months (95% confidence interval [CI]: 5-10 months), and median OS was 21 months (95% CI: 16-28 months) (Fig. 1). Fatigue and lethargy (49.1%), constipation (47.3%), and nausea (43.6%) were common. Grade 3-4 toxicities consisted mostly of increased aspartate aminotransferase (43.6%) and elevated alanine aminotransferase (38.2%) (Table 1). CONCLUSION Thalidomide and TACE were commonly associated with nonhematologic side effects, with fatigue and constipation being prominent. With a lack of clear therapeutic benefit, this combination is unlikely to be pursued for HCC.