Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours
Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours
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DOI：
10.1007/s00259-010-1631-x
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发表时间：
2011-02-01
影响因子：
9.1
通讯作者：
Turner, J. Harvey
中科院分区：
文献类型：
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作者：
Claringbold, Phillip G.;Brayshaw, Paul A.;Turner, J. Harvey
在这项 II 期研究中，我们研究了卡培他滨和 Lu-177-奥曲肽联合用药治疗播散性、进行性、不可切除的神经内分泌肿瘤 (NET) 的安全性和有效性。 纳入该研究的 33 名患者患有活检证实的 NET、In-111-奥曲肽闪烁扫描呈阳性且可通过 CT/MRI 测量疾病进展，他们将接受 4 次治疗。 每周 8 个周期的 7.8 GBq Lu-177-奥曲酯，每天 1,650 mg/m(2) 卡培他滨 14 天。在 33 名患者中，25 名完成了四个周期。 3-4 周时的最小短暂性骨髓抑制导致一名患者出现 3 级血小板减少症，但没有出现中性粒细胞减少症。不存在肾毒性。关键器官辐射剂量测定提供了每个周期肾脏 2.4 Gy 和肝脏 4.8 Gy 的剂量中值估计值，并显示累积剂量均低于毒性阈值。客观缓解率 (ORR) 为 24% 部分缓解 (PR)、70% 疾病稳定 (SD) 和 6% 疾病进展。中位随访 16 个月（范围 5-33 个月）时尚未达到中位无进展生存期和中位总生存期。 1 年和 2 年生存率分别为 91% (95% CI 75-98%) 和 88% (95% CI 71-96%)。加用卡培他滨放射增敏化疗不会增加 Lu-177-奥曲酸放射性肽治疗的最小毒性，并导致进展性转移患者的 ORR 为 24% PR 和 70% 轻微缓解或 SD NET。其中 94% 的患者获得了肿瘤控制和疾病稳定。
In this phase II study we investigated the safety and efficacy of combination capecitabine and Lu-177-octreotate for the treatment of disseminated, progressive, unresectable neuroendocrine tumours (NETs).Enrolled in the study were 33 patients with biopsy-proven NETs, positive In-111-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq Lu-177-octreotate 8-weekly, with 14 days of 1,650 mg/m(2) capecitabine per day.Of the 33 patients, 25 completed four cycles. Minimal transient myelosuppression at 3-4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia. Nephrotoxicity was absent. Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy, and showed cumulative doses all below toxic thresholds. Objective response rates (ORR) were 24% partial response (PR), 70% stable disease (SD) and 6% progressive disease. Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months (range 5-33 months). Survival at 1 and 2 years was 91% (95% CI 75-98%) and 88% (95% CI 71-96%), respectively.The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of Lu-177-octreotate radiopeptide therapy and led to an ORR of 24% PR and 70% minor response or SD in patients with progressive metastatic NETs. Tumour control and stabilization of disease was obtained in 94% of these patients.