A PHASE-I STUDY OF NEUROBLASTOMA WITH THE ANTIGANGLIOSIDE GD2 ANTIBODY 14.G2A
A PHASE-I STUDY OF NEUROBLASTOMA WITH THE ANTIGANGLIOSIDE GD2 ANTIBODY 14.G2A
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DOI：
10.1007/bf01756188
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发表时间：
1992-07-01
影响因子：
5.8
通讯作者：
NIETHAMMER, D
中科院分区：
文献类型：
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作者：
HANDGRETINGER, R;BAADER, P;NIETHAMMER, D
用小鼠单克隆抗体14对9例IV期神经母细胞瘤患者进行治疗。G2a，针对双胞脂苷GD2。抗体每天注射5-10天，总剂量为100 ~ 400 mg/m2。血清mAb 14的峰值水平。G2a范围为28 ~ 61 μ g/ml。在三名患者中获得的药代动力学数据表明，血清中mAb 14的消除。G2a符合双室模型，α -半衰期（t1/2- α）在0.66 h至1.98 h之间，β -半衰期（t1/2- β）在30.13 h至53.33 h之间。所有患者在治疗期间或治疗后不久均出现人抗（小鼠IgG）抗体反应。8例患者在治疗过程中补体成分C4持续下降，C3c初始降低，C3a初始升高，均提示补体级联激活。副作用包括过敏反应，如瘙痒、湿疹、荨麻疹和剧烈疼痛，主要发生在腹部和下肢，需要持续静脉注射吗啡。4名患者出现短暂性高血压，1名患者出现短暂性肾病综合征。3例患者接受辅助治疗，无法评估肿瘤反应。在剩下的6名患者中，2名完全缓解，2名部分缓解，2名对治疗没有反应。
Nine patients with neuroblastoma stage IV were treated with the murine monoclonal antibody 14.G2a, directed against disialoganglioside GD2. The antibody was injected daily for 5-10 days and the total applied dosage ranged between 100 mg/m2 and 400 mg/m2. The peak serum levels of mAb 14.G2a ranged from 28-mu-g/ml to 61-mu-g/ml. Pharmacokinetic data obtained in three patients indicated that the serum elimination of mAb 14.G2a fits a two-compartment model, with an alpha-half-time (t1/2-alpha) between 0.66 h and 1.98 h and a beta-half-time (t1/2-beta) between 30.13 h and 53.33 h. All patients presented with a human anti-(mouse IgG) antibody response either during or shortly after therapy. Eight patients showed a continuous decrease in complement component C4 during therapy, as well as an initial decrease in C3c and an initial increase in C3a, all suggesting an activation of the complement cascade. Side-effects consisted of allergic reactions like pruritus, exanthema, urticaria and of severe pain, predominantly located in the abdomen and lower extremities, which required the use of continuous intravenous morphine. Four patients additionally developed a transient hypertension and one patient experienced a transient nephrotic syndrome. Three patients were treated in an adjuvant setting and are not evaluable for tumor response. Of the remaining six patients, two had a complete remission, two showed a partial remission, and two patients did not respond to treatment.