医学
药代动力学
阿霉素
白细胞减少症
内科学
中性粒细胞减少症
化疗
转移性乳腺癌
药理学
癌症
乳腺癌
作者
Günter Emons,Manfred Kaufmann,G Gorchev,Valentina Tsekova,Carsten Gründker,Andreas R. Günthert,Lars Hanker,M Velikova,H. Sindermann,Jürgen Engel,Andrew V. Schally
标识
DOI:10.1016/j.ygyno.2010.08.003
摘要
Objectives Receptors for luteinizing hormone-releasing hormone (LHRH) can be utilized for targeted chemotherapy of cytotoxic LHRH analogs. The compound AEZS-108 (previously AN-152) consists of [D-Lys6]LHRH linked to doxorubicin. The objectives of this first study in humans with AESZ-108 were to determine the maximum tolerated dose and to characterize the dose-limiting toxicity, pharmacokinetics, preliminary efficacy, and hormonal effects. Methods The study included 17 women with histologically confirmed epithelial cancer of the ovary, endometrium, or breast that was metastatic or unresectable and for which standard curative or palliative measures could not be used or were no longer effective or tolerated. In each patient, immunohistochemistry of primary tumor or metastatic lesion confirmed that the tumors expressed LHRH receptors. Results One patient each received intravenous doses of 10, 20, 40, or 80 mg/m2 of AEZS-108, six received 160 mg/m2 and seven 267 mg/m2 at 3 week intervals. Dose-limiting leukopenia and neutropenia were observed at the highest dose. A total of 6 patients, 3 patients each in both upper dose groups, showed responses to AEZS-108. The half-life of AESZ-108 was estimated to be about 2 h. Conclusions The maximum tolerated dose of AESZ-108 in the absence of supportive medication is 267 mg/m2 and this dose is recommended as starting dose for therapeutic Phase II studies.
科研通智能强力驱动
Strongly Powered by AbleSci AI