West Howard L, Franklin Wilbur A, McCoy Jason, Gumerlock Paul H, Vance Ralph, Lau Derick H M, Chansky Kari, Crowley John J, Gandara David R
Swedish Cancer Institute/Puget Sound Oncology Consortium, Seattle, WA, USA.
J Clin Oncol. 2006 Apr 20;24(12):1807-13. doi: 10.1200/JCO.2005.04.9890.
Advanced bronchioloalveolar carcinoma (BAC) is a distinct subtype of non-small-cell lung cancer (NSCLC) for which there is currently no optimal therapy. Based on preclinical and clinical data suggesting relevance of the epidermal growth factor receptor (EGFR) axis in BAC, the Southwest Oncology Group initiated a phase II trial (S0126) to evaluate the EGFR tyrosine kinase inhibitor gefitinib in chemotherapy-naïve and chemotherapy-pretreated patients with advanced BAC.
A total of 136 eligible and assessable patients (101 untreated, 35 previously treated) received gefitinib 500 mg daily until progression or prohibitive toxicity.
The median age was 68.0 years (range, 34.3 to 88.6); 51% were female; 89% had a performance status (PS) of 0% or 1% and 11% had a PS of 2. The Response Evaluation Criteria in Solid Tumors response rate was 17%, with 6% complete responses (CRs) among 69 previously untreated patients with measurable disease, and 9% with no CRs among 22 pretreated patients. Median survival was 13 months for both chemo-naïve (95% CI, 8 to 18) and previously treated patients (95% CI, 6 to 17). Overall survival at 3 years was 23% (95% CI, 14% to 32%). Toxicity consisted mainly of rash and diarrhea, but 2% of patients died of presumed interstitial lung disease. Exploratory subset analyses revealed improved survival among women (P = .031), patients developing a rash (P = .003), never-smokers (P = .061), and patients with a PS of 0 or 1 (P = .015).
Gefitinib is an active agent in advanced stage BAC. Several subsets demonstrate significantly improved clinical outcomes.
晚期细支气管肺泡癌（BAC）是一种非小细胞肺癌（NSCLC）的独特亚型，目前尚无最佳治疗方法。基于临床前和临床数据表明表皮生长因子受体（EGFR）轴在BAC中的相关性，西南肿瘤协作组开展了一项II期试验（S0126），以评估EGFR酪氨酸激酶抑制剂吉非替尼在未经化疗和经化疗的晚期BAC患者中的疗效。
共有136例符合条件且可评估的患者（101例未治疗，35例先前接受过治疗）接受每日500 mg吉非替尼治疗，直至病情进展或出现难以耐受的毒性反应。
中位年龄为68.0岁（范围34.3至88.6岁）；51%为女性；89%的患者体能状态（PS）为0或1，11%的患者PS为2。实体瘤疗效评价标准的缓解率为17%，69例未经治疗且有可测量病灶的患者中6%完全缓解（CR），22例经治疗患者中9%无CR。未经化疗患者和先前接受过治疗患者的中位生存期均为13个月（95%CI，8至18和95%CI，6至17）。3年总生存率为23%（95%CI，14%至32%）。毒性反应主要包括皮疹和腹泻，但2%的患者死于疑似间质性肺病。探索性亚组分析显示，女性（P = 0.031）、出现皮疹的患者（P = 0.003）、从不吸烟者（P = 0.061）以及PS为0或1的患者（P = 0.015）的生存期有所改善。
吉非替尼是晚期BAC的一种有效药物。几个亚组显示临床结局有显著改善。
