Crvenkova S, Ivkovski Lj, Dimovski A, Kaeva B
University Radiotherapy and Oncology Clinic, Faculty of Medicine, Skopje, R. Macedonia.
Prilozi. 2012;33(1):303-11.
The aim of this study was to evaluate tumour response, QoL and adverse effects of erlotinib, EGFR tyrosine kinase inhibitor (TKI), as a second line therapy for patients with EGFR mutation in NSCLC, after failure of previous first-line therapy.
During the year 2010-11, 5 patients were enrolled in this study for testing EGFR mutations, after conditions for testing were created in Macedonia. We screened 5 patients for EGFR mutations by direct sequencing of exons 18 to 21, by retrospective analysis of their previous biopsy samples. Three of the patients were men and two of the patients were women. Two of the males were former smokers and one male and both females had never smoked. All the patients who were enrolled in the study had histologically proven adenocarcionoma. the patients started with erlotinib 150 mg, one tablet per day, after failure on previous first-line platinum-based chemotherapy, with or without surgery and radiotherapy. Assessment of tumour response was according to RECIST criteria at the follow-up visits every 4 weeks. We analysed tumour response from the beginning with erlotinib until tumuor progression or detection of severe toxicity. Assessment was performed only for those patients with EGFR mutations. Assessment of QoL was performed by patients' subjective answers, as subjective improvement and without subjective improvements. Adverse effects were applied according to WHO criteria.
Tissue was available for all 5 cases, two (40%) of which were found to harbour an EGFR mutation, identified as exon 19 deletions. Two patients responded to therapy. A complete response was seen in a female patient for 37 months. Progressive disease was the reason for stopping erlotinib after 37 months and starting third-line therapy. A partial response in one male patient was assessed for 30 months and is still in follow up. This patient is still alive and in good condition. The two patients reported subjective improvements during treatment with erlotinib. Skin rash was grade 2-3, and diarrhoea was grade 1-2. Both patients complained of hair loss, but without complete alopecia.
Considering our clinical results, we recommend target therapy with erlotinib for patients with NSCLC and EGFR mutations as a second-line treatment. Our excellent results encouraged us to require prospective tissue procurement for all patients in Macedonia. This may in fact require a shift in diagnostic practice, from the current emphasis on fine-needle aspiration, which often provides insufficient material for molecular analysis, to obtaining more substantial biopsies and to provide this treatment as first-line for selected patients.
本研究旨在评估厄洛替尼（一种表皮生长因子受体酪氨酸激酶抑制剂（TKI））作为非小细胞肺癌（NSCLC）表皮生长因子受体（EGFR）突变患者一线治疗失败后的二线治疗方案时的肿瘤反应、生活质量及不良反应。
在2010 - 2011年期间，马其顿创造了检测条件后，5名患者被纳入本研究以检测EGFR突变。我们通过对18至21外显子进行直接测序，对他们之前的活检样本进行回顾性分析，筛选了5名患者的EGFR突变。其中3名患者为男性，2名患者为女性。2名男性曾吸烟，1名男性和2名女性从不吸烟。所有纳入研究的患者均经组织学证实为腺癌。这些患者在之前一线铂类化疗失败后，无论是否接受过手术和放疗，均开始服用厄洛替尼150毫克，每日1片。每4周的随访中，根据实体瘤疗效评价标准（RECIST）评估肿瘤反应。我们分析了从开始使用厄洛替尼直至肿瘤进展或出现严重毒性期间的肿瘤反应。仅对那些EGFR突变的患者进行评估。生活质量评估通过患者的主观回答进行，分为主观改善和无主观改善。不良反应根据世界卫生组织标准进行评估。
所有5例患者均有可用组织，其中2例（40%）被发现存在EGFR突变，确定为19外显子缺失。2例患者对治疗有反应。1例女性患者出现完全缓解，持续37个月。疾病进展是37个月后停用厄洛替尼并开始三线治疗的原因。1例男性患者出现部分缓解，评估持续30个月，目前仍在随访中。该患者仍存活且状况良好。2例患者在厄洛替尼治疗期间均报告有主观改善。皮疹为2 - 3级，腹泻为1 - 2级。2例患者均抱怨有脱发，但未完全脱发。
考虑到我们的临床结果，我们推荐对NSCLC和EGFR突变患者使用厄洛替尼进行靶向治疗作为二线治疗。我们出色的结果促使我们要求为马其顿的所有患者进行前瞻性组织采集。这实际上可能需要改变诊断实践，从目前强调细针穿刺（其往往提供不足的材料用于分子分析）转变为获取更多实质性活检样本，并为选定患者提供一线治疗。
