gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Clinical phase I study of a (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) in patients with advanced cancers

Meeting Abstract

  • corresponding author presenting/speaker Clemens Unger - Tumor Biology Center, Freiburg, Deutschland
  • Michael Medinger - Tumor Biology Center
  • Simone Steinbild - Tumor Biology Center
  • Joachim Drevs - Tumor Biology Center
  • Brigritte Häring - Tumor Biology Center
  • Felix Kratz - Tumor Biology Center
  • Klaus Mross - Tumor Biology Center

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO458

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Unger et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: Doxorubicin is one of the most important anticancer drugs but therapy is associated with side effects such as myelosuppression, gastrointestinal disorders, mucositis, stomatitis, cumulative cardiotoxicity and extravasation. Serum albumin accumulates in solid tumors, thus coupling of an anticancer prodrug to albumin is a strategy for delivering the drug to its target site and preventing its diffusion into healthy tissue. An albumin-binding prodrug of doxorubicin with acid-sensitive properties, i.e. (6-maleimidocaproyl) hydrazone of doxorubicin (DOXO-EMCH), was developed to meet two features: (a) rapid and selective binding to the cysteine-34 position of endogenous albumin after intravenous administration, and (b) release of albumin-bound doxorubicin in the acidic environment of the tumor cell due to the incorporation of an acid-sensitive carboxylic hydrazone bond between the drug and the spacer molecule. Preclinically, DOXO-EMCH has shown superior antitumor efficacy and an improved toxicity profile compared to doxorubicin.

Methods: Cohorts of 3-6 patients with advanced cancer were treated with DOXO-EMCH (30 min iv infusion) d1 q3wk at dose levels of 20, 40, 80, 135, 150, 180, 200, 260, and 340 mg/m² doxorubicin equivalent. Assessment of tumor size was performed before and after every 2nd cycle.

Results: 41 pts were treated with DOXO-EMCH. DOXO-EMCH was well tolerated up to a dose of 200 mg/m2. DLT was observed in 2/6 patients at 340 mg/m² (grade 3 mucositis, grade 4 neutropenic fever). Mucositis (grade 1-2) and myelosuppression (1-2) were also the predominant toxicities at 260 mg/m2. No congestive heart failure occurred at any dose level. Significant tumor regressions were observed in patients with sarcoma, breast cancer, small cell lung cancer, parotis cancer and head & neck cancer at dose levels of 180 - 340 mg/m2.

Conclusion: The dose-limiting toxicities of DOXO-EMCH are myelotoxicity and stomatitis/mucositis which are also seen after doxorubicin monotherapy. DOXO-EMCH is an active anticancer agent able to induce clinical significant tumor regressions including complete and partial responses. Dose limiting toxicities were seen at 340 mg/m². The recommended dose for phase II studies is 260 mg/m² which represents a 3.5- to 4-fold increase compared to a standard dose of doxorubicin (60-75 mg/m²).