皮膚科 王修含醫生

研究論文摘要--晚期肺癌使用gefitinib(Iressa, 艾瑞莎)治療之皮膚表現與存活率分析

台大皮膚科  王修含 醫師

表皮細胞生長因子受體（EGFR）拮抗劑，例如gefitinib(即台灣稱為艾瑞莎Iressa的藥物)、erlotinib與cetuximab等標靶治療藥物，已被應用於治療癌症。其效度被認為與皮膚反應有關，但最重要的預後因子目前尚無定論。

台大皮膚科團隊與台大腫瘤科楊志新醫師合作進行本研究(DERMATOLOGICA SINICA 2011; 29, 13-18)，目的在探討gefitinib藥物造成的各種皮膚反應，並分析主要的治療預後因子。我們以回溯型研究的方法，分析68位以gefitinib(Iressa，艾瑞莎)治療晚期非小細胞型肺癌的病患，發現主要的皮膚反應為：
毛囊炎 (41.2%)、
皮膚乾燥 (38.2%)、
搔癢 (26.5%)、
甲溝炎 (16.2%)。


圖：晚期肺癌使用gefitinib(Iressa, 艾瑞莎)治療之皮膚表現- (A) 痤瘡樣毛囊炎(acneiform eruption)：本圖為脂漏性部位的膿皰與紅色丘疹 (B) 前額部位的膿皰 (C) 右前臂的皮膚乾燥(xerosis) (D) 的手指與腳趾部位具疼痛感的甲溝炎(paronychia)

單變項分析發現，甲溝炎為最重要的存活預後因子 (p = 0.0427)。
多變項分析顯示，雖然年老者存活率較低，但發生甲溝炎的老年病患，反而具有較好的預後 (p = 0.0050)；皮膚乾燥與甲溝炎的發生有正向相關性 (p = 0.0082)。



圖：晚期肺癌使用gefitinib(Iressa, 艾瑞莎)治療之皮膚表現與存活率關聯分析-使用Kaplan-Meier estimates分析發生甲溝炎(paronychia)之患者


圖：晚期肺癌使用gefitinib(Iressa, 艾瑞莎)治療之皮膚表現與存活率關聯分析-使用Kaplan-Meier estimates分析發生痤瘡樣毛囊炎(acneiform eruption)之患者


圖：晚期肺癌使用gefitinib(Iressa, 艾瑞莎)治療之皮膚表現與存活率關聯分析-使用Kaplan-Meier estimates分析發生搔癢反應(itching)之患者


圖：晚期肺癌使用gefitinib(Iressa, 艾瑞莎)治療之皮膚表現與存活率關聯分析-使用Kaplan-Meier estimates分析發生皮膚乾燥(xerosis)之患者

闡明這些皮膚反應的關係，能進一步提供我們關於皮膚表皮細胞生長因子受體之相關機制。

本論文詳細資料：Dermatologica Sinica. 2011; doi:10.1016/j.dsi.2011.02.003

Full Text: http://www.derm-sinica.com/article/S1027-8117%2811%2900013-9/fulltext

PDF檔：http://download.journals.elsevierhealth.com/pdfs/journals/1027-8117/PIIS1027811711000139.pdf

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DERMATOLOGICA SINICA 29 (2011) 13-18

王修含(Shiou-Han Wang),¹ 楊志新(Chih-Hsin Yang),² 邱顯清(Hsien-Ching Chiu),¹ 胡賦強(Fu-Chang Hu),³ 詹智傑(Chih-Chieh Chan),¹ 廖怡華(Yi-Hua Liao),¹ 陳小菁(Hsiao-Chin Chen),¹ 朱家瑜(Chia-Yu Chu)^1*

¹台灣大學醫學院附設醫院皮膚部(Department of Dermatology, National Taiwan University Hospital and College of Medicine, National Taiwan University)

²台灣大學醫學院附設醫院腫瘤醫學部(Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University)

³台灣大學醫學院暨公衛學院國家級卓越臨床試驗與研究中心(National Center of Excellence for General Clinical Trial and Research, National Taiwan University Hospital and College of Public Health, National Taiwan University)

ABSTRACT

Background/Purpose Epidermal growth factor receptor (EGFR) antagonists, such as gefitinib, erlotinib and cetuximab have been used in treating carcinomas. The efficacies have been proposed to correlate with skin reactions, but the most important predictive indicator is still unknown. Our aim was to investigate the types of skin toxicities and to analyze the major therapeutic predictive indicators in Taiwan.

Methods A retrospective analysis was used to study 68 patients with advanced non-small cell lung cancer receiving gefitinib.

Results Acneiform eruption (41.2%), xerosis (38.2%), pruritus (26.5%), and paronychia (16.2%) composed most of the skin reactions. The univariate analysis revealed paronychia the most substantial survival predictive indicator (p = 0.0427). In the multivariate analysis, older patients with paronychia have better prognosis (p = 0.0050). Women tended to develop paronychia (p = 0.1098). Xerosis positively correlated with paronychia (p = 0.0082).

Conclusion Paronychia is the most indicative survival predictive factor among the skin manifestations, and it correlates with age, gender and xerosis. Elucidation of the relationship between cutaneous reactions can provide information on the EGFR signaling mechanism of skin.

Table 1. Common skin toxicities in the 68 patients receiving gefitinib therapy.

Skin toxicities Median onset time (d) Men (%) (n=33) Women (%) (n=35) Total (%) (n=68)

Table 2. Median survival days and 1-year survival rate for each of the four main toxicities.

∗A two-sample log-rank test was conducted to compare the survival curves over the whole follow-up period.

Table 3. Multiple Cox’s proportional hazards model stratified by stage of disease for modeling the hazard rate of time to death (n=59).*

Risk factor Regression coefficient Standard error χ²p Hazard ratio

Age×male	0.0132	0.0068	3.7369	0.0532	1.013
Age×paronychia	−0.0283	0.0101	7.8727	0.0050	0.972
Male×xerosis	1.4487	0.5530	6.8641	0.0088	4.258

Table 4. Multiple logistic regression model for modeling the probability of having paronychia (n=59).*

∗Percentage of concordant pairs=68.4%; percentage of discordant pairs=10.6%; and percentage of tied pairs=21.0%; Hosmer and Lemeshow goodness-of-fit test χ²=0.3733 (with 2 degrees of freedom); p=0.8297>0.05.