1] Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea [2] Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
Br J Cancer. 2013 Sep 17;109(6):1414-9. doi: 10.1038/bjc.2013.470. Epub 2013 Aug 29.
Treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs) are still limited. We investigated the antitumour activity and safety profile of pazopanib--a multitarget drug with anti-angiogenic activity in patients with metastatic GEP NETs.
This was a nonrandomised, open-labeled, single-center phase II study. Pazopanib was orally administered at a dose of 800 mg daily continuously with a 28-day cycle. The primary end point was an objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST). The secondary end points were progression-free survival (PFS), overall survival (OS) and safety. An independent review of objective response was planned. The trial is registered with ClinicalTrials.gov, NCT number 01099540. Correlative biomarker analyses were performed.
Between April 2010 and February 2012, a total of 37 patients were enrolled. Thirty-two percent of the enrolled patients had pancreatic primary and 22% of the patients had colorectal primary NETs. This phase II study demonstrated an objective response rate of 18.9% (7 of the 37, 95% CI 8.0-35.2) and a disease control rate (CR+confirmed PR+stable disease) of 75.7% (28 of the 37, 95% CI, 58.8-88.2) in metastatic GEP NETs. The independent review demonstrated a higher overall response rate of 24.3% (95% CI, 11.8-41.2%) with nine confirmed PRs.
Pazopanib showed a comparable efficacy to other targeted agents not only in pancreatic NETs but also in NETs originating from gastrointestinal (GI) tract.
转移性胃肠胰神经内分泌肿瘤（GEP NET）患者的治疗选择仍然有限。我们研究了帕唑帕尼（一种具有抗血管生成活性的多靶点药物）在转移性 GEP NET 患者中的抗肿瘤活性和安全性。
这是一项非随机、开放性、单中心的 II 期研究。帕唑帕尼的剂量为 800mg 每日 1 次，连续给药，28 天为 1 个周期。主要终点是根据实体瘤反应评估标准（RECIST）的客观缓解率。次要终点是无进展生存期（PFS）、总生存期（OS）和安全性。计划进行客观缓解的独立评估。该试验在 ClinicalTrials.gov 注册，NCT01099540 号。进行了相关生物标志物分析。
2010 年 4 月至 2012 年 2 月期间，共纳入 37 例患者。入组患者中 32%为胰腺原发 NET，22%为结直肠原发 NET。这项 II 期研究显示，转移性 GEP NET 的客观缓解率为 18.9%（37 例中的 7 例，95%CI8.0-35.2），疾病控制率（CR+确认的 PR+稳定疾病）为 75.7%（37 例中的 28 例，95%CI，58.8-88.2）。独立评估显示，总缓解率更高，为 24.3%（95%CI，11.8-41.2%），有 9 例确认为 PR。
帕唑帕尼不仅在胰腺 NET 中，而且在源自胃肠道（GI）的 NET 中，与其他靶向药物具有相当的疗效。
