Royal Marsden Hospital, London, UK.
National Institute of Oncology, Budapest, Hungary.
Lancet Oncol. 2013 Oct;14(11):1077-1085. doi: 10.1016/S1470-2045(13)70154-2. Epub 2013 Sep 10.
Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer.
For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m(2) orally twice a day on days 1-14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939.
From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70-87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3-11·4] vs 5·1 months [4·2-6·3]; hazard ratio 0·53 [0·41-0·69]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]).
The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer.
F Hoffmann-La Roche.
老年患者在转移性结直肠癌的临床试验中往往代表性不足。我们旨在评估贝伐珠单抗联合卡培他滨与卡培他滨单药治疗转移性结直肠癌老年患者的疗效和安全性。
这是一项开放标签、随机 3 期临床试验，纳入了 280 例年龄 70 岁及以上、未经治疗、不可切除、转移性结直肠癌患者，这些患者不符合接受奥沙利铂或伊立替康为基础化疗方案的条件，通过交互式语音应答系统以 1:1 的比例随机分组，按体能状态和地理区域分层。治疗方案为卡培他滨（1000mg/m2 口服，每天 2 次，第 1-14 天）单药或联合贝伐珠单抗（7.5mg/kg 静脉注射，第 1 天），每 3 周给药一次，直至疾病进展、无法耐受的毒性作用或患者撤回同意。疗效分析基于意向治疗人群。主要终点为无进展生存期。该试验在 ClinicalTrials.gov 注册，编号为 NCT00484939。
2007 年 7 月 9 日至 2010 年 12 月 14 日，从 10 个国家的 40 个地点招募了中位年龄为 76 岁（范围为 70-87 岁）的 280 例患者。患者被随机分配接受贝伐珠单抗联合卡培他滨（n=140）或卡培他滨单药（n=140）治疗。与卡培他滨单药相比，贝伐珠单抗联合卡培他滨治疗的无进展生存期显著延长（中位 9.1 个月[95%CI 7.3-11.4] vs 5.1 个月[4.2-6.3]；风险比 0.53[0.41-0.69]；p<0.0001）。联合组中有 53 例（40%）患者发生 3 级或更高级别的治疗相关不良事件，卡培他滨组中有 30 例（22%）；联合组有 19 例（14%）和卡培他滨组有 11 例（8%）发生治疗相关严重不良事件。贝伐珠单抗或化疗引起的最常见的 3 级或更高级别的特殊关注不良事件是手足综合征（21 [16%] vs 9 [7%]）、腹泻（9 [7%] vs 9 [7%]）和静脉血栓栓塞事件（11 [8%] vs 6 [4%]）。联合组有 5 例患者和卡培他滨组有 4 例患者发生与治疗相关的死亡。贝伐珠单抗最常见的任何级别特殊关注不良事件是出血（34 [25%] vs 9 [7%]）。
贝伐珠单抗联合卡培他滨是一种有效且耐受良好的方案，可用于治疗转移性结直肠癌的老年患者。
罗氏制药。
