Stinchcombe Thomas E, Morris David E, Lee Carrie B, Moore Dominic T, Hayes D Neil, Halle Jan S, Rivera M Patricia, Rosenman Julian G, Socinski Mark A
Multidisciplinary Thoracic Oncology Program, 3009 Old Clinic Building CB 7305, Chapel Hill, NC 27599-7305, USA.
J Thorac Oncol. 2008 Mar;3(3):250-7. doi: 10.1097/JTO.0b013e3181653cf4.
Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT).
Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy.
Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively.
Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing.
综合治疗是不可切除的III期非小细胞肺癌（NSCLC）患者的标准治疗方法。吉非替尼在晚期NSCLC中具有活性，并且在临床前模型中，它可增强放射治疗的活性。我们研究了吉非替尼在联合三维胸部适形放疗（3D-TCRT）的综合治疗中的耐受性。
对体能状态良好的III期患者进行诱导化疗（卡铂曲线下面积[AUC]为5，伊立替康100mg/m²，紫杉醇175mg/m²，第1天和第22天），并给予培非格司亭支持，随后进行同步化疗（卡铂AUC 2，紫杉醇45mg/m²每周一次），并从第43天开始每日给予吉非替尼250mg，同时进行3D-TCRT至74Gy。
2004年3月至2006年1月期间，23例患者参加了该试验：中位年龄62岁（范围44-82岁），女性占52%，IIIA期占61%，体能状态0占61%，体重减轻≥5%占17%，91%接受了正电子发射断层扫描分期。给予培非格司亭支持的诱导化疗耐受性良好且有活性（部分缓解率为24%；疾病稳定率为76%；早期进展率为0%）。21例患者开始同步放化疗，20例患者完成了74Gy的治疗。同步放化疗的主要毒性为3级食管炎（19.5%）和心律失常（心房颤动）（9.5%）。中位无进展生存期和总生存期分别为9个月（95%置信区间[CI]：7-13个月）和16个月（95%CI：10-20个月）。
诱导化疗联合吉非替尼与3D-TCRT同步治疗具有可接受的毒性和耐受性，但生存结果令人失望。
