Belani Chandra P, Schreeder Marshall T, Steis Ronald G, Guidice Richard A, Marsland Thomas A, Butler Elizabeth H, Ramalingam Suresh S
Department of Medicine, Penn State Hershey Medical Center, Penn State Cancer Institute, Hershey, Pennsylvania 17033-0850, USA.
Cancer. 2008 Nov 1;113(9):2512-7. doi: 10.1002/cncr.23902.
Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody against the epidermal growth factor receptor, has demonstrated evidence of activity in nonsmall cell lung cancer (NSCLC). When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies. Therefore, a phase 2 study was conducted to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC.
Chemotherapy-naïve patients aged >or=18 years with stage IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400 mg/m(2) on Day 1 and 250 mg/m(2) on Days 8 and 15) plus docetaxel (at a dose of 75 mg/m(2) on Day 1) and carboplatin (area under the concentration vs time curve [AUC]=6 on Day 1) every 21 days for up to 6 cycles (graded according to the American Joint Committee on Cancer Staging System). Thereafter, patients without evidence of disease progression were continued on single-agent cetuximab for a maximum of 1 year or until disease progression. The primary endpoint was response rate.
Eighty patients were enrolled. The median number of cycles administered was 4 (range, 1-6 cycles). The objective response rate was 15.2%, with a median progression-free survival of 4.6 months and a median overall survival of 10.3 months. The salient grades 3 of 4 adverse events were neutropenia (30%), hypotension (3%), hypokalemia (4%), and hypomagnesemia (3%). Twenty-five patients received single-agent cetuximab (median duration, 12 weeks) and this was well tolerated.
The results of this large, multicenter, phase 3 study indicate that the novel combination of cetuximab with docetaxel and carboplatin demonstrate modest anticancer activity for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile.
西妥昔单抗是一种针对表皮生长因子受体的免疫球蛋白（Ig）G1嵌合单克隆抗体，已在非小细胞肺癌（NSCLC）中显示出活性证据。当与卡铂和多西他赛联合使用时（这是晚期NSCLC常用的治疗方案），西妥昔单抗在临床前研究中表现出协同作用。因此，开展了一项2期研究，以评估西妥昔单抗、卡铂和多西他赛联合治疗晚期NSCLC的疗效。
年龄≥18岁、初治的IIIB期（伴胸腔积液）或IV期NSCLC患者接受西妥昔单抗（第1天剂量为400mg/m²，第8天和第15天剂量为250mg/m²）加多西他赛（第1天剂量为75mg/m²）和卡铂（第1天浓度-时间曲线下面积[AUC]=6），每21天给药一次，最多6个周期（根据美国癌症联合委员会分期系统分级）。此后，无疾病进展证据的患者继续接受单药西妥昔单抗治疗，最长1年或直至疾病进展。主要终点为缓解率。
入组80例患者。给药周期的中位数为4（范围1-6个周期）。客观缓解率为15.2%，无进展生存期的中位数为4.6个月，总生存期的中位数为10.3个月。显著的3/4级不良事件为中性粒细胞减少（30%）、低血压（3%）、低钾血症（4%）和低镁血症（3%）。25例患者接受单药西妥昔单抗治疗（中位持续时间12周），耐受性良好。
这项大型多中心3期研究的结果表明，西妥昔单抗与多西他赛和卡铂的新联合方案对晚期和转移性NSCLC患者显示出适度的抗癌活性，且毒性可接受。
