Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, Japan,
Invest New Drugs. 2013 Oct;31(5):1265-74. doi: 10.1007/s10637-012-9910-y. Epub 2012 Dec 27.
Pancreatic neuroendocrine tumors (NETs) are rare but are frequently diagnosed at advanced stages and require systemic therapy.
This multicenter, open-label, phase II study evaluated sunitinib in Japanese patients with well-differentiated pancreatic NET. Patients received sunitinib 37.5 mg/day on a continuous daily dosing (CDD) schedule. The primary endpoint was clinical benefit rate (CBR; percentage of complete responses [CRs] plus partial responses [PRs] plus stable disease [SD] ≥ 24 weeks). Secondary endpoints included objective response rate (ORR), tumor shrinkage, progression-free survival (PFS) probability, safety, pharmacokinetics, and biomarkers.
Twelve patients received treatment. The CBR was 75 % (95 % confidence interval [CI], 43-94) and included 6 patients with a PR and 3 with SD. The ORR was 50 % (95 % CI, 21-79). PFS probability was 91 % (95 % CI, 54-99) at 6 months and 71 % (95 % CI, 34-90) at 12 months. Commonly reported treatment-emergent (all-causality), any-grade adverse events included diarrhea (n=10), hand-foot syndrome and hypertension (both n=8), fatigue and headache (both n=7), and neutropenia (n=6). No deaths on study were reported; one death due to disease progression occurred >28 days after end of treatment. Sunitinib on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Tumor responses in all 12 patients did not appear to correlate with decreases in chromogranin A levels.
Sunitinib 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese patients with unresectable, well-differentiated pancreatic NET. Commonly reported adverse events were consistent with the known safety profile of sunitinib.
胰腺神经内分泌肿瘤（NET）较为罕见，但常于晚期诊断，需要全身治疗。
这项多中心、开放标签、Ⅱ期研究评估了舒尼替尼在日本分化良好的胰腺 NET 患者中的疗效。患者接受舒尼替尼 37.5 mg/天，连续每日给药（CDD）方案。主要终点是临床获益率（CBR；完全缓解[CR]加部分缓解[PR]加稳定疾病[SD]持续≥24 周的比例）。次要终点包括客观缓解率（ORR）、肿瘤退缩、无进展生存期（PFS）概率、安全性、药代动力学和生物标志物。
12 例患者接受了治疗。CBR 为 75%（95%置信区间[CI]，43-94），包括 6 例 PR 和 3 例 SD。ORR 为 50%（95%CI，21-79）。6 个月时 PFS 概率为 91%（95%CI，54-99），12 个月时为 71%（95%CI，34-90）。常见的治疗相关（所有病因）、任何级别的不良事件包括腹泻（n=10）、手足综合征和高血压（均 n=8）、疲劳和头痛（均 n=7）以及中性粒细胞减少症（n=6）。研究中无死亡报告；1 例死亡发生于治疗结束后>28 天，与疾病进展相关。CDD 方案下舒尼替尼的药物浓度持续，无周期累积。所有 12 例患者的肿瘤反应似乎与嗜铬粒蛋白 A 水平降低无关。
CDD 方案下舒尼替尼 37.5 mg/天在日本不可切除、分化良好的胰腺 NET 患者中具有抗肿瘤活性。常见的不良事件与舒尼替尼已知的安全性特征一致。
