Kullmann F, Hollerbach S, Dollinger M M, Harder J, Fuchs M, Messmann H, Trojan J, Gäbele E, Hinke A, Hollerbach C, Endlicher E
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
Br J Cancer. 2009 Apr 7;100(7):1032-6. doi: 10.1038/sj.bjc.6604983. Epub 2009 Mar 17.
Targeting the epidermal growth factor receptor pathway in pancreatic cancer seems to be an attractive therapeutic approach. This study assessed the efficacy of cetuximab plus the combination of gemcitabine/oxaliplatin in metastatic pancreatic cancer. Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma. The primary end point was response according to RECIST. Patients received cetuximab 400 mg m(-2) at first infusion followed by weekly 250 mg m(-2) combined with gemcitabine 1000 mg m(-2) as a 100 min infusion on day 1 and oxaliplatin 100 mg m(-2) as a 2-h infusion on day 2 every 2 weeks. Between January 2005 and August 2006, a total of 64 patients (22 women (34%), 42 men (66%); median age 64 years (range 31-78)) were enrolled at seven study centres. On October 2007, a total of 17 patients were alive. Sixty-two patients were evaluable for baseline and 61 for assessment of response to treatment in an intention-to-treat analysis. Six patients had an incomplete drug combination within the first cycle of the treatment plan (n=4 hypersensitivity reactions to the first cetuximab infusion, n=2 refused to continue therapy). Reported grade 3/4 toxicities (% of patients) were leukopaenia 15%, anaemia 8%, thrombocytopaenia 10%, diarrhoea 7%, nausea 18%, infection 18% and allergy 7%. Cetuximab-attributable skin reactions occurred as follows: grade 0: 20%, grade 1: 41%, grade 2: 30% and grade 3: 10%. The intention-to-treat analysis of 61 evaluable patients showed an overall response rate of 33%, including 1 (2%) complete and 19 (31%) partial remissions. There were 31% patients with stable and 36% with progressive disease or discontinuation of the therapy before re-staging. The presence of a grade 2 or higher skin rash was associated with a higher likelihood of achieving objective response. Median time to progression was 118 days, with a median overall survival of 213 days. A clinical benefit response was noted in 24 of the evaluable 61 patients (39%). The addition of cetuximab to the combination of gemcitabine and oxaliplatin is well tolerated but does not increase response or survival in patients with metastatic pancreatic cancer.
靶向胰腺癌中的表皮生长因子受体通路似乎是一种有吸引力的治疗方法。本研究评估了西妥昔单抗联合吉西他滨/奥沙利铂治疗转移性胰腺癌的疗效。符合条件的受试者经组织学或细胞学诊断为转移性胰腺腺癌。主要终点是根据RECIST标准评估的反应。患者首次输注时接受西妥昔单抗400 mg/m²，随后每周接受250 mg/m²，联合吉西他滨1000 mg/m²在第1天进行100分钟输注，奥沙利铂100 mg/m²在第2天进行2小时输注，每2周重复一次。在2005年1月至2006年8月期间，共有64例患者（22例女性（34%），42例男性（66%）；中位年龄64岁（范围31 - 78岁））在7个研究中心入组。到2007年10月，共有17例患者存活。在意向性分析中，62例患者可用于基线评估，61例可用于评估治疗反应。6例患者在治疗计划的第一个周期内药物联合使用不完全（4例对首次西妥昔单抗输注有过敏反应，2例拒绝继续治疗）。报告的3/4级毒性（患者百分比）为白细胞减少15%、贫血8%、血小板减少10%、腹泻7%、恶心18%、感染18%和过敏7%。西妥昔单抗引起的皮肤反应情况如下：0级：20%，1级：41%，2级：30%，3级：10%。对61例可评估患者的意向性分析显示总缓解率为33%，包括1例（2%）完全缓解和19例（31%）部分缓解。31%的患者病情稳定，36%的患者病情进展或在重新分期前停止治疗。出现2级或更高等级的皮疹与获得客观反应的可能性更高相关。中位疾病进展时间为118天，中位总生存期为213天。在61例可评估患者中有24例（39%）观察到临床获益反应。在吉西他滨和奥沙利铂联合方案中添加西妥昔单抗耐受性良好，但并未提高转移性胰腺癌患者的反应率或生存率。
