A phase II study of radioimmunotherapy with intraventricular (131) I-3F8 for medulloblastoma.
A phase II study of radioimmunotherapy with intraventricular (131) I-3F8 for medulloblastoma.
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DOI：
10.1002/pbc.26754
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发表时间：
2018-01
影响因子：
3.2
通讯作者：
Cheung NV
中科院分区：
文献类型：
--
作者：
Kramer K;Pandit-Taskar N;Humm JL;Zanzonico PB;Haque S;Dunkel IJ;Wolden SL;Donzelli M;Goldman DA;Lewis JS;Lyashchenko SK;Khakoo Y;Carrasquillo JA;Souweidane MM;Greenfield JP;Lyden D;De Braganca KD;Gilheeney SW;Larson SM;Cheung NV
高风险和复发性髓母细胞瘤（MB）与显著的死亡率相关。鼠单克隆抗体3F 8靶向MB上的细胞表面二唾液酸神经节苷脂GD 2。我们在一项II期临床试验中检测了室间放射免疫治疗（cRIT）与脑室内131 I标记的3F 8在MB患者中的疗效、毒性和剂量测定。经组织病理学证实的高危或复发性MB患者有资格接受cRIT。在确定足够的脑脊液（CSF）流量后，患者接受2 mCi（其中Ci为居里）124 I-3F 8或131 I-3F 8核成像进行剂量测定，随后接受最多4次治疗性（10 mCi/剂量）131 I-3F 8注射。剂量测定估计值基于48小时内的连续CSF和血液采样以及连续成像扫描的感兴趣区域分析。疾病评估包括治疗前和治疗后脑/脊柱磁共振成像，治疗后第一年约每3个月一次，此后每6-12个月一次。43例患者共接受了167次注射; 42例患者的结局可评价。未发生给药相关死亡。与给药相关的毒性包括急性心动过缓伴嗜睡、头痛、疲乏和与化学性脑膜炎和张力障碍反应一致的CSF白细胞增多。总CSF吸收剂量为1，453 c戈伊（其中戈伊为戈瑞; 350.0- 2，784）。自cRIT首次给药的中位总生存期为24.9个月（95%置信区间[CI]：16.3-55.8）。放射学和细胞学缓解患者的死亡风险低于放射学可测量疾病患者（风险比：0.40，95% CI：0.18-0.88，P = 0.024）。使用131 I-3F 8的cRIT是安全的，对CSF具有良好的剂量测定，并且当使用传统方式添加到挽救治疗时，可能在维持高风险或复发性MB的缓解方面具有临床效用。
High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular131I-labeled 3F8 in patients with MB on a phase II clinical trial. Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) 124I-3F8 or 131I-3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) 131I-3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region-of-interest analyses on serial imaging scans. Disease evaluation included pre- and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6–12 months thereafter. Forty-three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment-related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0–2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3–55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18–0.88, P = 0.024). cRIT with 131I-3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high-risk or recurrent MB.
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影响因子：
11.5
作者：
Kadoch, Cigall;Li, Jing;Rubenstein, James L.
通讯作者：
Rubenstein, James L.
影响因子：
45.3
作者：
Cheung, Nai-Kong V.;Cheung, Irene Y.;Modak, Shakeel
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Modak, Shakeel
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15.9
作者：
Dunkel, Ira J.;Gardner, Sharon L.;Finlay, Jonathan L.
通讯作者：
Finlay, Jonathan L.
影响因子：
6.2
作者：
Shih, Chie-Schin;Hale, Gregory A.;Fouladi, Maryam
通讯作者：
Fouladi, Maryam
影响因子：
3.9
作者：
Kramer, K;Cheung, NKV;Gillio, AP
通讯作者：
Gillio, AP