標靶化療(anti-EGFR TKI) 對肺癌(NSCLC)有效性: 皮疹(skin rash) 是一個指標 !!!

皮疹可能预示抗EGFR治疗肺癌有效 发布时间：2012-7-31 来源：爱唯医学意大利肿瘤学家Petrelli Fausto博士等人研究发现，采用酪氨酸激酶抑制剂厄洛替尼或吉非替尼治疗非小细胞肺癌(NSCLC)时，发生皮疹可能是个好兆头。这项研究发表在《肺癌》(Lung Cancer)杂志7月16日在线版上。皮肤反应(尤其是丘疹脓疱皮疹)是抗表皮生长因子受体(EGFR)治疗的最常见不良反应，原因是表皮基底层和基底上层中的未分化和增殖性角质细胞中有EGFR表达。一旦发生皮疹则应治疗，以免引起患者不适和带来继发感染的风险。但已有部分研究提示，皮肤毒性与临床收益之间有关。为了进一步明确皮疹与疗效的关联，研究者从文献中检索出了17项相关的前瞻性试验和7个病例系列，共涉及超过3,000例患者。经过汇总分析，研究者发现，发生皮疹的患者36%对治疗产生应答，而无皮疹或仅有轻度皮疹的患者仅26%有应答。与无皮疹的患者相比，发生2~4级皮疹的患者获得应答的几率显著增高(7% vs. 42%)。不论是使用厄洛替尼还是吉非替尼，皮疹均与疾病进展风险[危险比(HR)，0.50]或死亡风险(HR，0.30)降低显著相关。研究者指出，他们无法确定受试者的EGFR状态，因此可以认为：在治疗数周后发生皮疹，可能是EGFR突变状态不明患者治疗有效的早期标志。根据这一判断，假如患者的突变分析结果不明，研究者建议"不妨先试用抗EGFR酪氨酸激酶抑制剂治疗，如果数周内未出现皮疹就停药"。而且，对于影像学检查提示治疗有效的患者，"发生皮疹算是一颗定心丸"。 

Relationship between skin rash and outcome in non-small-cell lung cancer patients treated with anti-EGFR tyrosine kinase inhibitors: A literature-based meta-analysis of 24 trials. Petrelli Fausto, Borgonovo Karen, Cabiddu Mary, Veronica Lonati and Barni Sandro Lung Cancer () (2012)   PMID 22795701

BACKGROUND: Dermatological toxicity, usually in the form of acneiform rash, is frequently observed in non-small-cell lung cancer (NSCLC) patients treated with anti-EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs). The objective of this review was to assess the predictive value of skin rash for outcome in patients with NSCLC treated with erlotinib and gefitinib.

METHODS: We searched PubMed for articles reporting a correlation of skin rash with survival, progression and response rate. In total, 349 prospective or retrospective studies presenting data regarding patient outcome and skin toxicity were screened. Hazard ratios (HRs) with 95% confidence intervals for progression and survival and risk ratios (RRs) for response rate were obtained from these publications and pooled in a meta-analysis.

RESULTS: This meta-analysis included 24 publications (17 prospective trials and 7 retrospective case series). Skin rash was found to be an independent predictive factor for survival (HR: 0.30; p<0.00001) and progression (HR: 0.50; p<0.00001). In addition, patients who developed grade 2-4 rash were more likely to respond to treatment respect to patients with no rash (42% vs. 7%). The result for survival meta-analysis appears to be similar for gefitinib and erlotinib.

CONCLUSION: These results are noteworthy, because patients with severe skin rash may be reassured over treatment outcome Skin rash during treatment with anti-EGFR TKIs for NSCLC represents a significantly strong predictor of the efficacy in particular for patients with unknown EGFR mutation status.