Division of Medical Oncology, Experimental Therapeutics Program, The Pancreas Center at Columbia, New York Presbyterian-Columbia University Medical Center, New York, NY 10032, USA.
Cancer Chemother Pharmacol. 2013 Mar;71(3):663-70. doi: 10.1007/s00280-012-2055-z. Epub 2013 Jan 31.
We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ).
A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR™ (100%), chemotherapy (61%), and hepatic chemoembolization (50%). Patients received capecitabine at 600 mg/m(2) orally twice daily on days 1-14 (maximum 1,000 mg orally twice daily) and TMZ 150-200 mg/m(2) divided into two doses daily on days 10-14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle.
Using RECIST parameters, 1 patient (5.5%) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5%) achieved a partial response (PR), and 4 patients (22.2%) had stable disease (SD). Total response rate was 61%, and clinical benefit (responders and SD) was 83.2%. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3-18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28-140 months). The only grade 3 toxicity was thrombocytopenia (11%). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths.
CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.
我们评估了卡培他滨和替莫唑胺（CAPTEM）在转移性神经内分泌肿瘤（NETs）患者中的疗效和安全性，这些患者的肿瘤已转移至肝脏。该方案是基于我们对类癌细胞系的研究，这些细胞系显示出与替莫唑胺（TMZ）顺序特异性给药联合应用时具有协同细胞毒性作用，5-氟尿嘧啶的剂量为 5-氟尿嘧啶（5-FU）。
对 18 例转移性 NETs 患者进行回顾性分析，这些患者的肿瘤已转移至肝脏，且对每月 60mg 的善宁长效释放剂（Sandostatin LAR）（100%）、化疗（61%）和肝动脉化疗栓塞（50%）均已耐药。患者接受卡培他滨 600mg/m2 口服，每日 2 次，第 1-14 天（最大剂量为每日 2 次口服 1000mg）；替莫唑胺 150-200mg/m2，每日 2 次，第 10-14 天，每 28 天为一个周期。每 2 个周期进行影像学检查，每 1 个周期检测血清肿瘤标志物。
采用 RECIST 参数，1 例（5.5%）中肠类癌患者获得手术证实的完全病理缓解（CR），10 例（55.5%）患者获得部分缓解（PR），4 例（22.2%）患者疾病稳定（SD）。总缓解率为 61%，临床获益（包括缓解和 SD）为 83.2%。在接受 CAPTEM 治疗的 4 例类癌患者中，1 例患者获得 CR，1 例患者获得 PR，1 例患者获得 SD，1 例患者发生疾病进展。无进展生存期的中位数为 14.0 个月（11.3-18.0 个月）。从诊断为肝转移开始的中位总生存期为 83 个月（28-140 个月）。唯一的 3 级毒性是血小板减少症（11%）。没有 4 级毒性、住院、机会性感染、发热性中性粒细胞减少症或死亡。
在先前治疗进展的分化良好的转移性 NET 患者中，CAPTEM 具有高活性、良好的耐受性，并可能延长生存期。
