XELOX联合沙利度胺-线治疗转移性结直肠癌的Ⅱ期随机对照研究

A Randomized Control PhaseⅡTrial of the Combination of XELOX and Thalidomide as the First-line Treatment for Metastatic Colorectal Cancer

目的:评价XELOX方案(奥沙利铂+卡培他滨)联合沙利度胺一线治疗晚期转移性结直肠癌(MCRC)的疗效及安全性。方法:89例符合入组条件的晚期转移性结直肠癌患者随机分为治疗组和对照组治疗组44例接受XELOX方案联合沙利度胺治疗,对照组45例仅接受XELOX方案化疗每21d为1个周期,每个病例至少治疗2个周期。主要研究无进展生存期,其次研究客观有效率、疾病控制率,并观察药物安全性及患者的生活质量结果:治疗组的无进展生存期为5.6个月,对照组为5.2个月,差异无统计学意义(P=0.307);客观有效率两组间无统计学差异(34.1%vs 26.7%,P=0.446);XELOX基础上加用沙制度胺后显著提高了疾病控制率(63.6%vs 42.2%,P=0.043)。治疗组伴有肝转移的24例患者中有2例治疗后达到可手术切除标准,而对照组伴有肝转移的23例患者则无1例达到标准。应用沙利度胺治疗的患者Ⅲ～Ⅳ级便秘发生率显著升高(20.5%vs4.4%,P=0.022),但未造成治疗中断;嗜睡发生率升高,但无统计学差异(13.6%vs 4.4%,P=0.130)。患者的生活质量两组间无统计学差异结论:在XELOX方案基础上加用沙利度胺一线治疗晚期结直肠癌耐受性良好并可显著提高疾病控制率,但未能提高无进展生存期。

Objective： To evaluate the efficacy and safety of the combination of the XELOX regimen （oxaliplatin plus capecitabine） and thalidomide as the first-line treatment for metastatic colorectal cancer （ MCRC ）. Methods： A total of 89 patients with MCRC who fulfilled all predetermined criteria were randomly assigned to the treatment and control group. The 44 patients in the treatment group received a combination of the XELOX regimen and thalidomide. The 45 patients in the control group received only the XELOX regimen. Each patient received at least two cycles （ 1 cycle = 21 d ） of treatment. The primary endpoint was progression-free survival （ PFS ）, and the second endpoints were objective response rate （ ORR ） as well as disease control rate （ DCR ）. Drug safety and quality of life were also assessed. Results： The median PFS of the treatment and control groups were 5.6 and 5.2 months, respectively. The difference did not have statistical significance （ P = 0.307 ）. The ORR of the 2 groups also had no statistical difference （ 34.1% vs. 26.7%, P = 0.446 ）. The addition of thalidomide to XELOX significantly improved the DCR （ 63.6% vs. 42.2%, P= 0.043 ）. Among the 24 patients with hepatic metastasis in the treatment group, 2 patients reached the surgical criteria after treatment. None of the patients in the control group did. Grades 3-4 constipation in patients treated with thalidomide was significantly elevated （ 20.5% vs. 4.4%, P = 0.022 ）, but did not warrant drug discontinuation. The incidence rate of lethargy was elevated, but the difference was not statistically significant （ 13.6% vs. 4.4%, P = 0.130 ）. The quality of life between the 2 groups had no statistical difference. Conclusion： A combination of XELOX and thalidomide as the first-line treatment in MCRC patients was well-tolerated. Statistically significant improvements were achieved for the DCR, but not for PFS.