Immunoembolization of Malignant Liver Tumors, Including Uveal Melanoma, Using Granulocyte-Macrophage Colony-Stimulating Factor
Immunoembolization of Malignant Liver Tumors, Including Uveal Melanoma, Using Granulocyte-Macrophage Colony-Stimulating Factor
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DOI：
10.1200/jco.2008.16.0705
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发表时间：
2008-11-20
影响因子：
45.3
通讯作者：
Sullivan, Kevin L.
中科院分区：
文献类型：
--
作者：
Sato, Takami;Eschelman, David J.;Sullivan, Kevin L.
目的我们进行了一项 I 期研究，探讨粒细胞巨噬细胞集落刺激因子 (GM-CSF；沙格司亭) 免疫栓塞治疗恶性肝肿瘤（主要是原发性葡萄膜黑色素瘤患者的肝转移）的可行性和安全性。 患者和方法 39 例无法手术切除的恶性肝肿瘤患者入组，其中 34 例为原发性葡萄膜黑色素瘤患者。肝动脉栓塞伴随着每 4 周输注剂量递增的 GM-CSF（25 至 2,000 μg）。主要终点包括剂量限制性毒性和最大耐受剂量（MTD）。监测完成两个治疗周期的患者的肝脏抗肿瘤反应。还监测了患者的存活率。结果MTD没有达到2000μg的剂量水平，并且没有与治疗相关的死亡。 31 名可评估的葡萄膜黑色素瘤患者表现出 2 例完全缓解、8 例部分缓解以及 10 例肝转移出现稳定疾病。转移性葡萄膜黑色素瘤意向治疗患者的中位总生存期为 14.4 个月。多变量分析表明，女性、高剂量 GM-CSF（>= 1,500 μg）以及肝转移的消退（完全缓解和部分缓解）与较长的总生存期相关。此外，高剂量的GM-CSF与肝外部位的无进展生存期延长相关。结论GM-CSF免疫栓塞对于原发性葡萄膜黑色素瘤肝转移患者是安全可行的。令人鼓舞的初步疗效和安全性结果值得对转移性葡萄膜黑色素瘤进行更多临床研究。
PurposeWe conducted a phase I study to investigate the feasibility and safety of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for malignant liver tumors, predominantly hepatic metastases from patients with primary uveal melanoma.Patients and MethodsThirty-nine patients with surgically unresectable malignant liver tumors, including 34 patients with primary uveal melanoma, were enrolled. Hepatic artery embolization accompanied an infusion of dose-escalated GM-CSF (25 to 2,000 mu g) given every 4 weeks. Primary end points included dose-limiting toxicity and maximum tolerated dose (MTD). Patients who completed two cycles of treatments were monitored for hepatic antitumor response. Survival rates of patients were also monitored.ResultsMTD was not reached up to the dose level of 2,000 mu g, and there were no treatment-related deaths. Thirty-one assessable patients with uveal melanoma demonstrated two complete responses, eight partial responses, and 10 occurrences of stable disease in their hepatic metastases. The median overall survival of intent-to-treat patients who had metastatic uveal melanoma was 14.4 months. Multivariate analyses indicated that female sex, high doses of GM-CSF (>= 1,500 mu g), and regression of hepatic metastases (complete and partial responses) were correlated to longer overall survival. Moreover, high doses of GM-CSF were associated with prolonged progression-free survival in extrahepatic sites.ConclusionImmunoembolization with GM-CSF is safe and feasible in patients with hepatic metastasis from primary uveal melanoma. Encouraging preliminary efficacy and safety results warrant additional clinical study in metastatic uveal melanoma.