Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Lancet Oncol. 2010 Jan;11(1):48-54. doi: 10.1016/S1470-2045(09)70333-X. Epub 2009 Nov 20.
Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([(18)F]FDG)-PET correlate with clinical outcome.
Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m(2) (10 mg/m(2) per min) and oxaliplatin 85 mg/m(2) (2-h infusion). [(18)F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231.
35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7.0 months (95% CI 5.3-10.3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [(18)F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUV(max)) after two cycles of treatment (5.72 [SD 2.01] at baseline; 3.73 [SD 1.88] after two cycles; p<0.0001). These changes were more pronounced in patients with partial response or stable disease than those with progressive disease (24 patients, -2.80 [SD 1.95] vs five patients, 1.41 [SD 3.13]; p=0.009). Change in SUV(max) was a significant predictor of PFS (HR 1.35, 1.14-1.60, p=0.0006) and overall survival (1.25, 1.05-1.50, p=0.01).
GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUV(max) on [(18)F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival.
Genentech Oncology and Sanofi-Aventis.
先前的两项 2 期研究显示，在晚期胆道癌（BTC）患者中，吉西他滨联合奥沙利铂（GEMOX）具有抗肿瘤活性。在这项 2 期研究中，我们评估了贝伐珠单抗联合 GEMOX（GEMOX-B）在晚期 BTC 患者中的疗效和安全性，并研究了氟代脱氧葡萄糖 ([（18）F]FDG)-PET 变化与临床结局的相关性。
在 28 天周期的第 1 天和第 15 天，给予晚期可测量 BTC 患者以下治疗：贝伐珠单抗 10mg/kg，随后给予吉西他滨 1000mg/m²（10mg/m²/分钟）和奥沙利铂 85mg/m²（2 小时输注）。在基线和第二个周期结束时进行 [(18)F]FDG-PET 扫描。主要终点是无进展生存期（PFS）。疗效和安全性分析采用意向治疗。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00361231。
35 名患者入组并可评估疗效和毒性。中位 PFS 为 7.0 个月（95%CI 5.3-10.3），6 个月时 PFS 为 63%（47-79），低于目标 70%。3-4 级毒性反应包括中性粒细胞减少症（n=7）、丙氨酸氨基转移酶浓度升高（n=5）、周围神经病（n=5）和高血压（n=5）。在两次治疗周期后，[(18)F]FDG-PET 扫描显示最大标准摄取值（SUV(max)）显著下降（基线时为 5.72[SD 2.01]；两次周期后为 3.73[SD 1.88]；p<0.0001）。与进展性疾病患者相比，部分缓解或疾病稳定患者的变化更为明显（24 名患者，-2.80[SD 1.95]；5 名患者，1.41[SD 3.13]；p=0.009）。SUV(max)的变化是 PFS（HR 1.35，1.14-1.60，p=0.0006）和总生存期（1.25，1.05-1.50，p=0.01）的显著预测因子。
GEMOX-B 在晚期 BTC 患者中具有抗肿瘤活性，安全性可耐受。治疗后 [(18)F]FDG-PET 扫描中 SUV(max)的降低与疾病控制以及 PFS 和总生存期的延长相关。
基因泰克肿瘤学和赛诺菲-安万特。
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