索拉非尼治疗中晚期肝癌相关的手足皮肤反应与疗效的关系

Relationship between sorafenib-associated hand-food skin reaction and efficacy in treatment of advanced hepatocellular carcinoma

目的探讨索拉非尼治疗中晚期肝癌相关的手足皮肤反应（HFRS）与疗效的关系。方法分析广东省人民医院肿瘤介入科2008年5月至2011年6月51例索拉非尼联合经导管肝动脉化疗栓塞术（TACE）治疗的中晚期肝癌患者资料，比较HFRS0级、1—2级、3级三组患者间的疾病控制率（DCR）、中位无疾病进展生存期（mPFS）、中位生存期（mOS）的差异，Cox模型分析影响PFS的因素。结果13／51例未出现HFRS（即0级），38／51例出现HFRS，其中，1～2级27例，3级11例，三组DCR分别为38．5％、70．4％、90．9％，0级组比1～3级组的DCR：38．5％比76．3％，P=0．031，1—2级组比3级组，P=0．352；三组的mPFS分别为2．8（95％CI1．6—4．0）、4．5（95％CI1．3—7．7）和12．8（95％CI3．7—21．9）个月，0级组比1～2级组，P=0．019，相关风险比（HR）：2．8（95％CI1．3—6．3），P=0．010，0级组比3级组，P〈0．01，HR：6．6（95％CI2．3～19．0），P〈0．01，差异均有统计学意义，1—2级组比3级组，P=0．054；三组mOS分别为8．5（95％CI5．9—11．1）、13．0（95％CI10．1～15．9）和25．4个月，两两比较，P〈0．05。结论HFRS可作为索拉非尼治疗中晚期肝癌临床疗效的预示指标，但是疗效是否随HFRS严重程度的递增而增加尚待论证。

Objective To investigate the link between the antitumor efficacy of sorafenib and its cutaneous side effects in advanced hepatocellular carcinoma（HCC）. Methods We retrospectively analyzed the incidence of hand-foot skin reactions （HFRS） of 51 patients with advanced HCC who treated by sorafenib combined with transcatheter arterial chemoembolization （TACE）, comparing tumor disease control rate （DCR）, median progression free survival （mPFS） and median overall survival （mOS） in the different severity HFRS groups. The Cox proportional hazard model was applied to the multivariate survival analysis for the PFS. Results Fifty-one HCC patients treated with sorafenib combined with TACE were included in this study. 13/51 without HFRS（grade 0）, 38/51 developed at all grade 1 -3,27 developed at grade 1 -2,11 developed at grade 3. The DCR were 38. 5% ,70. 4% and 90. 9% in the three groups （ P 〈 0. 05 ）. Group grade 0 vs grade 1 - 3,P = 0. 031, the difference had statistical significance. Group grade 1 - 2 vs grade 3, P =0. 352,the difference had no statistical significance. The mPFS were 2. 8 months（95% CI 1.6 -4. 0）, 4. 5（95% CI 1.3 -7.7） months and 12. 8（95% CI 3.7 -21.9） months（P 〈0.05） ,group grade 0 vs grade 1 - 2, P = 0. 019, HR （ hazard ratio） ：2. 8 （ 95 % CI 1.3 - 6. 3 ）, P = 0. 010, group grade 0 vs grade 3, P 〈 0. 01, HR 6. 6 （95 % C1 2. 3 - 19. 0）, P 〈 0. 01, group grade 1 - 2 vs grade 3, P = 0. 054 ; the three groups＇ mOS were 8.5 months（95% CI 5.9 - 11.1 ）, 13.0 （95% CI 10. 1 - 15.9 ） months and 25.4 months, P 〈 0. 05, there were statistically significant differences between the any two groups. Conclusions HFRS should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy, but it has yet to be demonstrated whether the efficacy increasing with the severity of HFRS or not.