CHU Reims, Reims, France.
Anticancer Res. 2011 Jun;31(6):2271-81.
The feasibility of an alternating regimen of BIBF 1120, a potent, oral, triple angiokinase inhibitor, and afatinib (BIBW 2992), a potent ErbB family blocker, was explored in patients with advanced pretreated colorectal cancer (CRC).
Patients received repeated courses of alternating 7-day treatment periods, first with BIBF 1120 250 mg twice daily and then afatinib 50 mg once daily. The primary endpoint was the objective response rate; the incidence/severity of adverse events (AEs) and pharmacokinetics (PK) were determined.
Forty-six patients (≥4 prior lines, most anti-VEGF and/or -EGFR pretreated) received BIBF 1120 and afatinib. No objective responses were observed; the best response was stable disease in 20 patients (43.5%). Seven patients (15.2%) remained progression-free for ≥16 weeks. Median progression-free survival was 1.9 months; median overall survival was 5.5 months. The most frequent drug-related AEs were diarrhoea (80.4%), asthenia (47.8%), nausea (43.5%) and rash (41.3%). PK assessments did not show obvious alterations for either drug.
Weekly alternating administration of BIBF 1120 and afatinib is feasible; however, its efficacy was limited in this highly palliative patient population.
探索在既往接受过治疗的晚期结直肠癌（CRC）患者中，交替使用强效口服三血管激酶抑制剂 BIBF 1120 和强效 ErbB 家族阻滞剂阿法替尼（BIBW 2992）的方案的可行性。
患者接受重复的 7 天治疗期交替治疗，首先是每日两次 250mg 的 BIBF 1120 和随后每天一次 50mg 的阿法替尼。主要终点是客观缓解率；不良事件（AE）的发生率/严重程度和药代动力学（PK）也被确定。
46 名（≥4 线治疗，大多数抗 VEGF 和/或抗 EGFR 预处理）患者接受了 BIBF 1120 和阿法替尼治疗。未观察到客观缓解，最佳缓解是 20 名患者（43.5%）的疾病稳定。7 名患者（15.2%）无进展生存期≥16 周。中位无进展生存期为 1.9 个月；中位总生存期为 5.5 个月。最常见的药物相关 AE 是腹泻（80.4%）、乏力（47.8%）、恶心（43.5%）和皮疹（41.3%）。PK 评估未显示两种药物有明显的变化。
BIBF 1120 和阿法替尼每周交替给药是可行的；然而，在这种高度姑息性的患者人群中，其疗效有限。
