使用(111)铟/(90)钇-2IT-BAD-m170进行转移性前列腺癌的放射免疫治疗。

Radioimmunotherapy with (111)In/(90)Y-2IT-BAD-m170 for metastatic prostate cancer.

作者信息

O'Donnell R T, DeNardo S J, Yuan A, Shen S, Richman C M, Lara P N, Griffith I J, Goldstein D S, Kukis D L, Martinez G S, Mirick G R, DeNardo G L, Meyers F J

机构信息

Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis Medical Center, Sacramento, California 95816,

出版信息

Clin Cancer Res. 2001 Jun;7(6):1561-8.

PMID:11410491

Abstract

PURPOSE

Over 31,000 Americans die of androgen-independent metastatic prostate cancer each year. New strategies that do not involve hormonal manipulation but instead recognize the biochemical and molecular characteristics of prostate cancer are needed. Radioimmunotherapy (RIT) uses a tumor-specific monoclonal antibody to deliver systemic, targeted radiation to cancer. The objectives of this Phase I study of (111)In-2IT-BAD-m170 (for imaging) and (90)Y-2IT-BAD-m170 (for therapy) were to determine the toxicity and maximum tolerated dose (MTD), the specificity for targeting metastatic prostate cancer, and the efficacy for palliation of pain.

EXPERIMENTAL DESIGN

M170 is a mouse monoclonal antibody that targets adenocarcinomas. Patients with adequate renal and liver function, rising prostate-specific antigen, and androgen-independent metastatic prostate cancer were eligible. After estimation of dosimetry and pharmacokinetics with (111)In-2IT-BAD-m170, a single dose of (90)Y-2IT-BAD-m170 (0.185, 0.370, 0.555, or 0.740 GBq/m(2)) was administered to cohorts of three patients. Pain was assessed objectively by questionnaires before and for 8 weeks after RIT; weekly prostate-specific antigen levels were obtained for 2 months after RIT.

RESULTS

The MTD of (90)Y-2IT-BAD-m170 was 0.740 GBq/m(2) for patients that had up to 10% of the axial skeleton involved with prostate cancer. Toxicity was almost exclusively confined to reversible myelosuppression. Metastatic prostate cancer was targeted by (111)In-2IT-BAD-m170 in all 17 patients. The mean radiation dose delivered to 39 bone and 18 nodal metastases by (90)Y-2IT-BAD-m170 was 10.5 Gy/GBq (range 2.8-25.1). Thirteen of 17 patients reported pain before (90)Y-2IT-BAD-m170; 7 of these 13 had a partial or complete resolution of pain that lasted an average of 4.3 weeks.

CONCLUSIONS

This study determined the MTD of (111)In/(90)Y-2IT-BAD-m170 in patients with metastatic prostate cancer. The drugs were well tolerated, targeted metastases, and temporarily palliated pain.

摘要

目的

每年有超过31000名美国人死于雄激素非依赖性转移性前列腺癌。需要新的策略，不涉及激素操纵，而是识别前列腺癌的生化和分子特征。放射免疫疗法（RIT）使用肿瘤特异性单克隆抗体将全身靶向辐射递送至癌症部位。这项关于（111）铟-2IT-BAD-m170（用于成像）和（90）钇-2IT-BAD-m170（用于治疗）的I期研究的目的是确定毒性和最大耐受剂量（MTD）、靶向转移性前列腺癌的特异性以及缓解疼痛的疗效。

实验设计

M170是一种靶向腺癌的小鼠单克隆抗体。肾功能和肝功能正常、前列腺特异性抗原升高且患有雄激素非依赖性转移性前列腺癌的患者符合条件。在用（111）铟-2IT-BAD-m170估计剂量学和药代动力学后，给每组三名患者单次注射（90）钇-2IT-BAD-m170（0.185、0.370、0.555或0.740 GBq/m²）。在放射免疫疗法之前和之后8周通过问卷客观评估疼痛；在放射免疫疗法后2个月每周获取前列腺特异性抗原水平。

结果

对于前列腺癌累及轴向骨骼达10%的患者，（90）钇-2IT-BAD-m170的MTD为0.740 GBq/m²。毒性几乎完全局限于可逆性骨髓抑制。在所有17名患者中，（111）铟-2IT-BAD-m170均靶向转移性前列腺癌。（90）钇-2IT-BAD-m170对39处骨转移和18处淋巴结转移的平均辐射剂量为10.5 Gy/GBq（范围2.8 - 25.1）。17名患者中有13名在接受（90）钇-2IT-BAD-m170治疗前报告有疼痛；这13名患者中有7名疼痛部分或完全缓解，平均持续4.3周。