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卵巢癌的腹腔内放射免疫疗法:I-131标记单克隆抗体的药代动力学、毒性及疗效

Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies.

作者信息

Stewart J S, Hird V, Snook D, Sullivan M, Hooker G, Courtenay-Luck N, Sivolapenko G, Griffiths M, Myers M J, Lambert H E

机构信息

Imperial Cancer Research Fund, Royal Postgraduate Medical School, London, England.

出版信息

Int J Radiat Oncol Biol Phys. 1989 Feb;16(2):405-13. doi: 10.1016/0360-3016(89)90337-4.

Abstract

Thirty-six patients with ovarian cancer were treated with intraperitoneal I-131 labeled monoclonal antibodies to tumor associated antigens. The activity of I-131 administered was increased from 20 mCi to 158 mCi and the pharmacokinetics and toxicity evaluated. Five patients who had developed HAMA (Human Antimouse Antibodies) were retreated, and the pharmacokinetics and toxicity of the first and second treatment compared. Patients receiving their first therapy (HAMA negative), had a maximum of 25% (range 19.8-39.8%) of the injected activity in their circulation. This was accompanied by severe marrow suppression at I-131 activities over 120 mCi. The 5 HAMA positive patients had only 5% injected activity in the systemic circulation (range 3.8-6%), with rapid urinary excretion and neglible marrow suppression. In 31 patients with assessable disease there were no responses in 8 patients with gross disease (nodules greater than 2 cms), partial responses in 2 out of 15 patients with nodules less than 2 cms, and complete responses in 3 out of 6 patients with microscopic disease. The non specific radiation dose to the peritoneal cavity was estimated to be less than 500 cGy by lithium fluoride TLD, and could not be expected to account for the responses seen.

摘要

36例卵巢癌患者接受了腹腔内注射I-131标记的肿瘤相关抗原单克隆抗体治疗。给予的I-131活度从20mCi增加到158mCi,并对其药代动力学和毒性进行了评估。对5例产生人抗鼠抗体(HAMA)的患者进行了再次治疗,并比较了首次和第二次治疗的药代动力学和毒性。接受首次治疗(HAMA阴性)的患者,其循环中注射活度的最大值为25%(范围19.8 - 39.8%)。当I-131活度超过120mCi时,会伴有严重的骨髓抑制。5例HAMA阳性患者的全身循环中仅含5%的注射活度(范围3.8 - 6%),尿液排泄迅速,骨髓抑制可忽略不计。在31例可评估病情的患者中,8例有肉眼可见病变(结节大于2cm)的患者无反应,15例结节小于2cm的患者中有2例部分缓解,6例微小病变患者中有3例完全缓解。通过氟化锂热释光剂量计估计,腹腔的非特异性辐射剂量小于500cGy,预期这并不能解释所观察到的反应。

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