Medical Clinic II, University Hospital Frankfurt, Frankfurt/Main, Germany.
Medical Clinic II, University Hospital Frankfurt, Frankfurt/Main, Germany.
Eur J Cancer. 2015 Jan;51(1):27-36. doi: 10.1016/j.ejca.2014.10.010. Epub 2014 Nov 5.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumours and is still associated with a poor prognosis in advanced disease. To improve the standard therapy with gemcitabine, we initiated a prospective randomised phase-II trial with gemcitabine (GEM) versus gemcitabine plus sunitinib (SUNGEM) based on data of in vitro trials and phase-I data for the combination treatment. The rational of adding sunitinib was its putative antiangiogenic mechanism of action.
A total of 106 eligible patients with locally advanced, unresectable or metastatic PDAC without previous system therapy were randomised to receive GEM at a dosage of 1.000mg/m(2) d1, 8, 15 q28 versus a combination of SUNGEM at a dosage of GEM 1.000mg/m(2) d1+8 and sunitinib 50mg p.o. d1-14, q21d. The primary end-point was progression free survival (PFS), secondary end-points were overall survival (OS), toxicity and overall response rate (ORR).
The confirmatory analysis of PFS was based on the intend-to-treat (ITT) population (N=106). The median PFS was 13.3 weeks (95% confidence interval (95%-CI): 10.4-18.1 weeks) for GEM and 11.6 weeks for SUNGEM (95%-CI: 7.0-18.0 weeks; p=0.78 one-sided log-rank). The ORR was 6.1% (95%-CI: 0.7-20.2%) for GEM and for 7.1% (95%-CI: 0.9-23.5%) for SUNGEM (p=0.87). The median time to progression (TTP) was 14.0 weeks (95%-CI: 12.4-22.3 weeks) for GEM and 18.0 weeks (95%-CI: 11.3-19.3 weeks) for SUNGEM (p=0.60; two-sided log-rank). The median OS was 36.7 weeks (95%-CI: 20.6-49.0 weeks) for the GEM arm and 30.4 weeks (95%-CI: 18.1-37.6 weeks) for the SUNGEM (p=0.78, one-sided log-rank). In regard to toxicities, suspected SAEs were reported in 53.7% in the GEM arm and 71.2% in the SUNGEM arm. Grade 3 and 4 neutropenia was statistically significantly higher in the SUNGEM arm with 48.1% versus 27.8% in the GEM arm (p=0.045, two sided log-rank).
The combination SUNGEM was not sufficient superior in locally advanced or metastatic PDAC compared to GEM alone in regard to efficacy but was associated with more toxicity.
胰腺导管腺癌（PDAC）是最常见的恶性肿瘤之一，在晚期疾病中仍然预后不良。为了改善吉西他滨的标准治疗，我们根据体外试验数据和联合治疗的 I 期数据，启动了一项吉西他滨（GEM）与吉西他滨联合舒尼替尼（SUNGEM）的前瞻性随机 II 期试验。加入舒尼替尼的依据是其潜在的抗血管生成作用机制。
共纳入 106 例局部晚期、不可切除或转移性 PDAC 患者，既往无系统治疗，随机接受 GEM 剂量为 1000mg/m2 d1、8、15 q28 或 SUNGEM 剂量为 GEM 1000mg/m2 d1+8 和舒尼替尼 50mg po d1-14、q21d。主要终点是无进展生存期（PFS），次要终点是总生存期（OS）、毒性和总缓解率（ORR）。
PFS 的确认性分析基于意向治疗（ITT）人群（N=106）。GEM 组的中位 PFS 为 13.3 周（95%置信区间[95%-CI]：10.4-18.1 周），SUNGEM 组为 11.6 周（95%-CI：7.0-18.0 周；p=0.78 单侧对数秩）。GEM 组的 ORR 为 6.1%（95%-CI：0.7-20.2%），SUNGEM 组为 7.1%（95%-CI：0.9-23.5%）（p=0.87）。GEM 组的中位进展时间（TTP）为 14.0 周（95%-CI：12.4-22.3 周），SUNGEM 组为 18.0 周（95%-CI：11.3-19.3 周）（p=0.60；双侧对数秩）。GEM 组的中位 OS 为 36.7 周（95%-CI：20.6-49.0 周），SUNGEM 组为 30.4 周（95%-CI：18.1-37.6 周）（p=0.78，单侧对数秩）。关于毒性，GEM 组报告可疑严重不良事件（SAE）发生率为 53.7%，SUNGEM 组为 71.2%。GEM 组中性粒细胞 3 级和 4 级发生率明显高于 SUNGEM 组，分别为 48.1%和 27.8%（p=0.045，双侧对数秩）。
在局部晚期或转移性 PDAC 中，SUNGEM 联合治疗在疗效方面并不优于单独使用 GEM，但毒性更大。
