Hepato-Gastroenterology Unit, Cliniques Universitaires Saint-Luc Bruxelles, Bruxelles.
Ann Oncol. 2013 Nov;24(11):2824-9. doi: 10.1093/annonc/mdt337. Epub 2013 Aug 23.
Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression.
In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m(2) at week 1, then 250 mg/m(2)/week) and Gemcitabine (1 g/m(2) on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy.
Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect ≥grade 2 was associated with increased PFS (P = 0.05).
CONCLUSION(S): Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy. ClinicalTrials.gov Identifier: NCT00747097.
胆管癌是一种预后较差的罕见肿瘤，常表现为表皮生长因子受体过度表达。
在一项多中心的 II 期试验中，未经化疗的不可切除胆管癌患者接受西妥昔单抗（第 1 周 400mg/m2，然后每周 250mg/m2）和吉西他滨（第 1、8 和 15 天 1g/m2，每 4 周 1 次）治疗。主要终点是 6 个月时的无进展生存率（PFS），采用 Simon 两阶段设计。此外，我们评估了 KRAS 状态和皮肤毒性对疗效的影响。
共纳入 44 例患者（41%局部晚期/59%转移性）。中位年龄为 61.5 岁；ECOG PS 为 0（68%）或 1（32%）。6 个月 PFS 率为 47%。中位总生存期为 13.5 个月[95%置信区间（CI）9.8-31.8 个月]。9 例（20.4%）患者获得部分缓解，疾病控制率为 79.5%。3/4 级相关毒性为血液学毒性（52.2%）、皮疹（13.6%）和乏力（11.4%）。27 例患者中有 7 例发现 KRAS 突变，但与 PFS 无关。皮肤毒性≥2 级与 PFS 增加相关（P=0.05）。
本研究达到了主要终点，提示吉西他滨联合西妥昔单抗治疗胆管癌有活性。KRAS 状态与 PFS 无关，而皮肤毒性与疗效相关，可作为疗效的替代标志物。临床试验注册编号：NCT00747097。
