Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study
Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study
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DOI：
10.1007/s00259-018-4003-6
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发表时间：
2018-07-01
影响因子：
9.1
通讯作者：
Morgenstern, Alfred
中科院分区：
文献类型：
--
作者：
Autenrieth, Michael E.;Seidl, Christof;Morgenstern, Alfred
目的：卡介苗（BCG）治疗无效的膀胱原位癌（CIS）患者通常使用环磷酰胺治疗。因此，需要保留膀胱的新治疗选择。本研究的目的是调查的可行性，安全性和有效性的一种新的有针对性的α-发射体免疫治疗CIS后BCG治疗failure.Methods的试点研究进行了12例（年龄范围64-86岁，10名男性，两名女性）活检证实的膀胱癌的BCG治疗难治性。用偶联抗EGFR抗体的α-发射体Bi-213（366-821 MBq）的单次滴注（一名患者治疗两次）膀胱内治疗患者。本研究的主要目的是确定用Bi-213-免疫缀合物治疗的可行性并评价不良反应。治疗后8周及其后不同时间点的膀胱组织学检查显示治疗效果。结果研究证明膀胱内灌注靶向EGFR的Bi-213-免疫偶联物是可行的。未观察到不良反应，测定的所有血液和尿液参数均保持在正常范围内。12例患者中3例在治疗后44、30和3个月均未出现CIS，疗效满意。结论膀胱灌注抗EGFR单克隆抗体Bi-213具有良好的耐受性和治疗效果。重复滴注和/或滴注更高活性的Bi-213-免疫缀合物可能导致更好的治疗结果。计划进行I期临床试验。
Purpose Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Gu,rin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure.Methods A pilot study was conducted in 12 patients (age range 64-86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter Bi-213 coupled to an anti-EGFR antibody (366-821 MBq). The primary aims of the study were to determine the feasibility of treatment with the Bi-213-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter.Results The study proved that intravesical instillation of the Bi-213-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment.Conclusion Intravesical instillation of Bi-213-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the Bi-213-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned.