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Phase I clinical study of vascular targeting fluorescent cationic liposomes in head and neck cancer

  • Head and Neck
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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

The aim of this first-time-in-human non-randomized dose-escalating prospective phase I clinical trial was to analyze safety of two doses of fluorescent rhodamine-labeled cationic liposomes (LDF01) in head and neck squamous cell carcinoma (HNSCC). Patients had resectable UICC stadium I–IV A HNSCCs. LDF01 was administered before tumor resection under general anesthesia as an intravenous infusion with effective lipid doses of 0.5 or 2 mg/kg b.w., respectively. In addition to clinical monitoring for safety assessment, tumor biopsies were taken during the surgical procedure for fluorescence histological analysis. Eight patients were assigned to the two dose groups. During safety follow-up no clinically relevant adverse events occurred. Fluorescence histology revealed some evidence of favorable selectivity of LDF01 for tumor microvessels in the high-dose group. LDF01 is safe applied as infusion at both tested dose levels. Furthermore, LDF01 can be detected in the vicinity of tumor cells and could be assigned to the microvessel target in individual HNSSC cases. Detailed analysis of targeting properties of LDF01 has to be performed in upcoming clinical phase II trials.

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References

  1. Gold KA, Lee HY, Kim ES (2009) Targeted therapies in squamous cell carcinoma of the head and neck. Cancer 115(5):922–935. doi:10.1002/cncr.24123

    Article  PubMed  CAS  Google Scholar 

  2. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359(11):1116–1127

    Article  PubMed  CAS  Google Scholar 

  3. Christopoulos A, Ahn SM, Klein JD, Kim S (2011) Biology of vascular endothelial growth factor and its receptors in head and neck cancer: beyond angiogenesis. Head Neck 33(8):1220–1229. doi:10.1002/hed.21588

    Article  PubMed  Google Scholar 

  4. Bernier J, Bentzen SM, Vermorken JB (2009) Molecular therapy in head and neck oncology. Nat Rev Clin Oncol 6(5):266–277

    Article  PubMed  CAS  Google Scholar 

  5. Denekamp J (1982) Endothelial cell proliferation as a novel approach to targeting tumour therapy. Br J Cancer 45(1):136–139

    Article  PubMed  CAS  Google Scholar 

  6. Denekamp J (1999) The tumour microcirculation as a target in cancer therapy: a clearer perspective. Eur J Clin Invest 29(9):733–736

    Article  PubMed  CAS  Google Scholar 

  7. Thurston G, McLean JW, Rizen M, Baluk P, Haskell A, Murphy TJ, Hanahan D, McDonald DM (1998) Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice. J Clin Invest 101(7):1401–1413

    Article  PubMed  CAS  Google Scholar 

  8. Krasnici S, Werner A, Eichhorn ME, Schmitt-Sody M, Pahernik SA, Sauer B, Schulze B, Teifel M, Michaelis U, Naujoks K, Dellian M (2003) Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels. Int J Cancer 105(4):561–567

    Article  PubMed  CAS  Google Scholar 

  9. Augustin HG, Kozian DH, Johnson RC (1994) Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes. Bioessays 16(12):901–906. doi:10.1002/bies.950161208

    Article  PubMed  CAS  Google Scholar 

  10. Iozzo RV (2001) Heparan sulfate proteoglycans: intricate molecules with intriguing functions. J Clin Investig 108(2):165–167. doi:10.1172/JCI13560

    PubMed  CAS  Google Scholar 

  11. Ran S, Downes A, Thorpe PE (2002) Increased exposure of anionic phospholipids on the surface of tumor blood vessels. Cancer Res 62(21):6132–6140

    PubMed  CAS  Google Scholar 

  12. Schmitt-Sody M, Strieth S, Krasnici S, Sauer B, Schulze B, Teifel M, Michaelis U, Naujoks K, Dellian M (2003) Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy. Clin Cancer Res 9:2335–2341

    PubMed  CAS  Google Scholar 

  13. Eichhorn ME, Luedemann S, Strieth S, Papyan A, Ruhstorfer H, Haas H, Michaelis U, Sauer B, Teifel M, Enders G, Brix G, Jauch KW, Bruns CJ, Dellian M (2007) Cationic lipid complexed camptothecin (EndoTAG((R))-2) improves antitumoral efficacy by tumor vascular targeting. Cancer Biol Ther 6(6):920–929

    Article  PubMed  CAS  Google Scholar 

  14. Strieth S, Eichhorn ME, Sauer B, Schulze B, Teifel M, Michaelis U, Dellian M (2004) Neovascular targeting chemotherapy: encapsulation of paclitaxel in cationic liposomes impairs functional tumor microvasculature. Int J Cancer 110(1):117–124

    Article  PubMed  CAS  Google Scholar 

  15. Strieth S, Nussbaum CF, Eichhorn ME, Fuhrmann M, Teifel M, Michaelis U, Berghaus A, Dellian M (2008) Tumor-selective vessel occlusions by platelets after vascular targeting chemotherapy using paclitaxel encapsulated in cationic liposomes. Int J Cancer 122(2):452–460

    Article  PubMed  CAS  Google Scholar 

  16. Strieth S, Eichhorn ME, Werner A, Sauer B, Teifel M, Michaelis U, Berghaus A, Dellian M (2008) Paclitaxel encapsulated in cationic liposomes increases tumor microvessel leakiness and improves therapeutic efficacy in combination with Cisplatin. Clin Cancer Res 14(14):4603–4611

    Article  PubMed  CAS  Google Scholar 

  17. Lohr JM, Haas SL, Bechstein WO, Bodoky G, Cwiertka K, Fischbach W, Folsch UR, Jager D, Osinsky D, Prausova J, Schmidt WE, Lutz MP (2011) Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial. Ann Oncol. doi:10.1093/annonc/mdr379

    PubMed  Google Scholar 

  18. Eichhorn ME, Strieth S, Krasnici S, Sauer B, Teifel M, Michaelis U, Naujoks K, Dellian M (2004) Protamine enhances uptake of cationic liposomes in angiogenic microvessels. Angiogenesis 7(2):133–141

    Article  PubMed  CAS  Google Scholar 

  19. Kuenen BC, Levi M, Meijers JC, van Hinsbergh VW, Berkhof J, Kakkar AK, Hoekman K, Pinedo HM (2003) Potential role of platelets in endothelial damage observed during treatment with cisplatin, gemcitabine, and the angiogenesis inhibitor SU5416. J Clin Oncol 21(11):2192–2198

    Article  PubMed  CAS  Google Scholar 

  20. Fasol U, Frost A, Buchert M, Arends J, Fiedler U, Scharr D, Scheuenpflug J, Mross K (2012) Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis. Ann Oncol 23(4):1030–1036. doi:10.1093/annonc/mdr300

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank the patients, their families and caregivers, and all the personnel who contributed to patient care and data collection for this study. This study was supported by Munich Biotech AG, Neuried, Germany.

Conflict of interest

The authors deny any financial relationship with the organization that sponsored the research.

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Author notes

  1. Sebastian Strieth

    Present address: Department of Otorhinolaryngology, Goethe-University Frankfurt/M., Theodor-Stern-Kai 7, 60590, Frankfurt/M., Germany

Authors and Affiliations

  1. Department of Otorhinolaryngology, University of Munich (LMU), Munich, Germany

    Christoph Dunau, Donata Strelczyk, Uta Tschiesner & Marc Dellian

  2. Department of Otorhinolaryngology, University of Lübeck, Lübeck, Germany

    Kristina Kolbow & Barbara Wollenberg

  3. Institute of Pathology, University of Aachen (RWTH), Aachen, Germany

    Ruth Knuechel

  4. Munich Biotech AG, Neuried, Germany

    Uwe Michaelis

  5. Department of Anesthesiology, University of Munich (LMU), Munich, Germany

    Hannelore Ledderose

  6. Department of Surgery, Campus Großhadern, University of Munich (LMU), Munich, Germany

    Martin E. Eichhorn

Authors
  1. Sebastian Strieth
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  2. Christoph Dunau
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  7. Martin E. Eichhorn
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Correspondence to Sebastian Strieth.

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Strieth, S., Dunau, C., Kolbow, K. et al. Phase I clinical study of vascular targeting fluorescent cationic liposomes in head and neck cancer. Eur Arch Otorhinolaryngol 270, 1481–1487 (2013). https://doi.org/10.1007/s00405-012-2185-2

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  • DOI: https://doi.org/10.1007/s00405-012-2185-2

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