Reck Martin, Gatzemeier Ulrich
Onkologischer Schwerpunkt, Krankenhaus Grosshansdorf, Zentrum für Thoraxchirurgie, Studienkoordination, Wöhrendamm 80, D-22927 Grosshansdorf, Germany.
Lung Cancer. 2005 Oct;50(1):107-14. doi: 10.1016/j.lungcan.2005.05.006.
Gefitinib is the first approved EGFR tyrosine-kinase inhibitor indicated for the treatment of patients with locally advanced (IIIB) or metastatic NSCLC after failure of platinum-based first-line therapy and docetaxel chemotherapy. Following rapid approval in Japan and accelerated approval based on phase-II results in the US, a large compassionate-use program has been set up in parallel to extended phase-III testing. Offering therefore access to state-of-the-art therapy to patients who are not candidates for clinical studies; Iressatrade mark EAP allows physicians to test the new EGFR inhibitor across a heterogeneous patient population characteristic for advanced NSCLC.
After having treated 240 patients at the Grosshansdorf hospital, we have retrospectively analysed the efficacy and tolerability of 250 mg/day gefitinib in patients showing a long-term tumor control. We reviewed the patient records of 14 patients with advanced NSCLC that received daily gefitinib for at least 9 months.
Long-term tumor control, defined as confirmed objective tumor response for at least 6 months or disease stabilisation for above 9 months, was observed in chemo-naive patients as well as in fourth-line therapy patients for the latter ones independently of the composition of prior chemotherapy. Most patients (9/14) with such a lasting benefit were female; patients' histology was in most cases uniform: adenocarcinomas were dominant in women and bronchioloalveolar carcinoma in men. Patients with moderate to severe dyspnoea benefited from a measurable improvement of their respiratory capacity. No cumulative toxicity was observed; characteristic side-effects for gefitinib as grades 1-2 diarrhoea or mild to moderate skin toxicity were well manageable.
For 14 (6%) out of 240 patients with patterns of diffuse disseminated metastatic disease, gefitinib offered a lasting tumor control with a disease progression-free survival interval between 9 and 25 months. In parallel to therapy, patients' performance status (PS) could be conserved or even improved in many cases. Patients with lung function impairment, as well as patients with other disease-related symptoms obtained additional therapy benefits.
吉非替尼是首个获批的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，用于治疗在铂类一线治疗及多西他赛化疗失败后出现的局部晚期（IIIB期）或转移性非小细胞肺癌（NSCLC）患者。继在日本迅速获批以及基于II期试验结果在美国加速获批之后，在开展III期扩展试验的同时，已并行设立了一个大型同情用药项目。因此，对于那些不适合参加临床研究的患者而言，可使其获得最先进的治疗；易瑞沙商标的扩大可及项目（EAP）使医生能够在具有晚期NSCLC特征的异质性患者群体中对这种新型EGFR抑制剂进行试验。
在格罗斯汉斯多夫医院治疗了240例患者之后，我们回顾性分析了每日服用250毫克吉非替尼对显示长期肿瘤控制的患者的疗效和耐受性。我们查阅了14例晚期NSCLC患者的病历，这些患者接受了至少9个月的每日吉非替尼治疗。
在初治患者以及四线治疗患者中均观察到了长期肿瘤控制，后者被定义为确诊的客观肿瘤反应至少持续6个月或疾病稳定超过9个月，且与先前化疗的组成无关。大多数获得这种持久疗效的患者（9/14）为女性；患者的组织学类型在大多数情况下较为一致：腺癌在女性中占主导，细支气管肺泡癌在男性中占主导。有中度至重度呼吸困难的患者呼吸能力得到了可测量的改善。未观察到累积毒性；吉非替尼的典型副作用如1 - 2级腹泻或轻度至中度皮肤毒性易于控制。
在240例弥漫性播散性转移性疾病患者中，有14例（6%）患者通过吉非替尼实现了持久的肿瘤控制，无疾病进展生存期在9至25个月之间。在治疗的同时，在许多情况下患者的体能状态（PS）得以维持甚至改善。肺功能受损的患者以及有其他与疾病相关症状的患者获得了额外的治疗益处。
