Cancer Therapy

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Vascular targeting by EndoTAG™-1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer

  1. Martin E. Eichhorn1,2,†,*,
  2. Ivan Ischenko1,
  3. Siiri Luedemann2,
  4. Sebastian Strieth2,3,
  5. Armine Papyan1,
  6. Alexander Werner4,
  7. Hermann Bohnenkamp5,
  8. Eric Guenzi5,
  9. Gerhard Preissler1,
  10. Uwe Michaelis5,
  11. Karl-Walter Jauch1,
  12. Christiane J. Bruns1,
  13. Marc Dellian3

Article first published online: 20 AUG 2009

DOI: 10.1002/ijc.24846

Issue

International Journal of Cancer

International Journal of Cancer

Volume 126, Issue 5, pages 1235–1245, 1 March 2010

Additional Information

How to Cite

Eichhorn, M. E., Ischenko, I., Luedemann, S., Strieth, S., Papyan, A., Werner, A., Bohnenkamp, H., Guenzi, E., Preissler, G., Michaelis, U., Jauch, K.-W., Bruns, C. J. and Dellian, M. (2010), Vascular targeting by EndoTAG™-1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer. Int. J. Cancer, 126: 1235–1245. doi: 10.1002/ijc.24846

Author Information

  1. 1

    Department of Surgery, Klinikum Grosshadern, University of Munich, Munich, Germany

  2. 2

    Walter Brendel Center for Experimental Medicine, University of Munich, Munich, Germany

  3. 3

    Department of Otorhinolaryngology, Klinikum Grosshadern, University of Munich, Munich, Germany

  4. 4

    Bioservice Scientific Laboratories GmbH, Planegg, Germany

  5. 5

    Medigene AG, Planegg, Germany

  1. †

    Fax: +4989-2443-40591

*Department of Surgery, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany

Publication History

  1. Issue published online: 27 DEC 2009
  2. Article first published online: 20 AUG 2009
  3. Accepted manuscript online: 20 AUG 2009 12:00AM EST
  4. Manuscript Accepted: 3 AUG 2009
  5. Manuscript Received: 21 FEB 2009

Funded by

  • The FöFoLe Research Program, University of Munich. Grant Number: Nr. 379
  • The Bavarian Research Foundation. Grant Number: Nr. AZ-652-05

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Keywords:

  • tumor angiogenesis;
  • vascular targeting therapy;
  • cationic liposomes;
  • paclitaxel;
  • combination therapy

Abstract

Cationic lipid complexed paclitaxel (EndoTAG™-1) is a novel vascular targeting agent for the treatment of cancer. Here, the aim was to investigate intratumoral drug distribution after EndoTAG™-1 therapy and analyze the impact of EndoTAG™-1 scheduling on antitumoral efficacy. The therapeutic effect of EndoTAG™-1 in combination with conventional gemcitabine or cisplatin therapy was evaluated in L3.6pl orthotopic pancreatic cancer and a subcutaneous Lewis lung (LLC-1) carcinoma model. Oregon Green paclitaxel encapsulated in cationic liposomes in combination with intravital fluorescence microscopy clearly exhibited delivery of the drug by EndoTAG™-1 to the tumor endothelium, whereas Oregon Green paclitaxel dissolved in cremophor displayed an interstitial distribution pattern. The therapeutic efficacy of EndoTAG™-1 was critically dependent on the application schedule with best therapeutic results using a metronomic rather than a maximum tolerated dose application sequence. The combination of EndoTAG™-1 therapy and cytotoxic chemotherapy significantly enhanced antitumoral efficacy in both tumor models. Interestingly, only EndoTAG™-1 in combination with gemcitabine was able to inhibit the incidence of metastasis in pancreatic cancer. In conclusion, vascular targeting tumor therapy by EndoTAG™-1 combined with standard small molecular chemotherapy results in markedly enhanced antitumoral efficacy. Therefore, this combination represents a promising novel strategy for clinical cancer therapy.

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