肝癌放射治疗中同时给予沙利度胺的 II 期研究。

Phase II study of concomitant thalidomide during radiotherapy for hepatocellular carcinoma.

机构信息

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.

出版信息

Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):817-25. doi: 10.1016/j.ijrobp.2010.10.067. Epub 2011 Jan 27.

DOI:10.1016/j.ijrobp.2010.10.067

PMID:21277098

Abstract

PURPOSE

Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients.

METHODS AND MATERIALS

A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only.

RESULTS

No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 ± 48.9 vs. 148 ± 6.2 days, p = .15), or median overall survival (258 ± 45.6 vs. 241 ± 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-α levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT completion was a significant predictor of the overall survival of HCC patients receiving RT.

CONCLUSIONS

Despite the acceptable toxicity, thalidomide provided no additional benefit for HCC patients undergoing RT.

摘要

目的

沙利度胺已被证明在晚期肝细胞癌（HCC）患者中具有抗肿瘤活性。本研究的目的是确定沙利度胺联合放疗（RT）治疗是否与 HCC 患者可接受的毒性和改善的临床结果相关。

方法和材料

共纳入 24 例患者接受 RT 联合沙利度胺治疗。总剂量为 50 Gy，在 5 周内以 2 Gy 分次给予。沙利度胺在 RT 前 3 天开始每天服用 100 mg，每日两次，直至出现不可接受的毒性或疾病进展。在治疗前后采集血样以测量血管生成因子和细胞因子的水平。将接受联合治疗的患者的结果与仅接受 RT 的 18 例 HCC 患者的结果进行比较。

结果

两组患者的临床参数无显著差异，除了基线白细胞介素-6 水平，联合组更高（p=0.05）。与沙利度胺使用相关的最常见毒性是皮疹（54.2%）、嗜睡（37.5%）和便秘（33.3%）。两组的客观缓解率（55.6% vs. 58.3%，p=0.48）、无进展生存期中位数（182±48.9 与 148±6.2 天，p=0.15）或总生存期中位数（258±45.6 与 241±38.6 天，p=0.16）均无显著差异。沙利度胺在 RT 期间显著抑制血清碱性成纤维细胞生长因子水平（p=0.03），并在较小程度上抑制白细胞介素-6 和肿瘤坏死因子-α水平。在多因素分析中调整其他潜在预后因素后，只有基线白细胞介素-6 水平和 RT 期间的干细胞衍生因子-1独立预测无进展生存期。RT 完成后 1 个月血清干细胞衍生因子-1水平降低是预测接受 RT 的 HCC 患者总生存期的显著指标。