Division of Hematology/Oncology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
Br J Cancer. 2014 Jul 29;111(3):430-6. doi: 10.1038/bjc.2014.343. Epub 2014 Jun 24.
Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer.
Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0-2 were treated with panitumumab 6 mg kg(-1), GEM 1000 mg m(-2) (10 mg m(-2) min(-1)) and OX 85 mg m(-2) on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival.
Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5-24 months) and median overall survival 20.3 months (95% CI 9-25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%.
The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer.
目前的数据表明，铂类联合化疗是胆管癌的标准一线治疗。表皮生长因子受体（EGFR）抑制剂已被证明对多种胃肠道恶性肿瘤有效；并且在 KRAS 野生型结肠癌的遗传亚型中显示出了特定的优势。我们报告了帕尼单抗联合吉西他滨（GEM）和奥沙利铂（OX）作为 KRAS 野生型胆管癌的一线治疗。
组织学证实的、未经治疗的、不可切除或转移性 KRAS 野生型胆管或胆囊腺癌患者，ECOG 表现状态 0-2，接受帕尼单抗 6mg/kg，GEM 1000mg/m²（10mg/m²·min）和 OX 85mg/m²，每 28 天周期的第 1 天和第 15 天。主要目标是根据 RECIST 标准 v.1.1 确定客观缓解率。次要目标是评估毒性、无进展生存期（PFS）和总生存期。
31 名患者在三个机构接受了至少一个周期的治疗，28 名患者有可测量的疾病。缓解率为 45%，疾病控制率为 90%。中位 PFS 为 10.6 个月（95%CI 5-24 个月），中位总生存期为 20.3 个月（95%CI 9-25 个月）。最常见的 3/4 级不良事件为贫血 26%、白细胞减少 23%、疲劳 23%、周围神经病变 16%和皮疹 10%。
吉西他滨、奥沙利铂和帕尼单抗联合治疗 KRAS 野生型转移性胆管癌显示出令人鼓舞的疗效，在胆管癌中需要进一步进行遗传分层和靶向治疗的努力。
