Phase I and pharmacokinetic study of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin

Unger, Clemens and Häring, Brigitte and Medinger, Michael and Drevs, Joachim and Steinbild, Simone and Kratz, Felix and Mross, Klaus. (2007) Phase I and pharmacokinetic study of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin. Clinical Cancer Research, 13 (16). pp. 4858-4866.

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Official URL: http://edoc.unibas.ch/43932/

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The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that shows superior antitumor efficacy in murine tumor models and a favorable toxicity profile in mice, rats, and dogs compared with doxorubicin. The purpose of the phase I study was to characterize the toxicity profile of DOXO-EMCH, establish a recommended dose for phase II studies, and assess potential anticancer activity.; A starting dose of 20 mg/m2 doxorubicin equivalents was chosen. Forty-one patients with advanced cancer disease were treated with an i.v. infusion of DOXO-EMCH once every 3 weeks at a dose level of 20 to 340 mg/m2 doxorubicin equivalents.; Treatment with DOXO-EMCH was well tolerated up to 200 mg/m2 without manifestation of drug-related side effects. Myelosuppression (grade 1-2) and mucositis (grade 1-2) were the predominant adverse effects at dose levels of 260 mg/m2 and myelosuppression (grade 1-3) as well as mucositis (grade 1-3) were dose limiting at 340 mg/m2. No cardiac toxicity was observed. Of 30 of 41 evaluable patients, 12 patients (40%) had progressive disease, 15 patients (57%) had stable disease, and 3 patients (10%) had a partial remission.; DOXO-EMCH showed a good safety profile and was able to induce tumor regressions in tumor types known to be anthracycline-sensitive tumors, such as breast cancer, small cell lung cancer, and sarcoma. The recommended doxorubicin equivalent dose for phase II studies is 260 mg/m2.
Faculties and Departments:03 Faculty of Medicine
UniBasel Contributors:Medinger, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for Cancer Research
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Oct 2017 07:50
Deposited On:04 Oct 2017 07:50

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