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Dermatux: phase IV trial of Cetuximab plus FOLFIRI in first-line metastatic colorectal cancer receiving a pre-defined skin care

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

Cetuximab-induced skin rash Gd3+ occurs in ≥16% patients (pts) (Heinemann et al., Lancet Oncol 15(10):1065–1075, 2014; Van Cutsem et al. J Clin Oncol 27(19):3117–25; 2009b). Survival, response, and toxicity parameters were re-evaluated under a pre-defined skin prophylaxis consistent of vitamin K1 ointment and oral doxycycline.

Methods

This is a national, multicenter, phase 4, first-line mCRC (K-RAS wt) trial. Pts received irinotecan 180 mg/m² (d1), FA 400 mg/m² (d1), 5-FU 400 mg/m² (d1), 5-FU 2400 mg/m² (d1–2), and cetuximab [400 mg/m² (d1), and then 250 mg/m² qw], prophylactic 0.1% vitamin K1 ointment qd, and oral doxycycline 100 mg bid. Primary objective: 1-year PFS rate; secondary objectives: skin side-effects (grade, onset), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) time, and overall survival (OS) time and safety.

Results

Twenty centers recruited 55 patients. Recruitment started Q1 2011 and ended Q3 2013 due to slow accrual. Characteristics were in line with CRYSTAL trial except for age and colonic location. 1-year PFS rate was 25.9%, mOS 21.8 months (m), and mPFS 8.5 m. ORR was 63.0%, DCR 77.8%. Rash Gd2+ occurred in 42.6% [median onset was 4.0 weeks (w)]; paronychia Gd2+ occurred in 22.2% (median onset 15.4w.); skin fissures Gd2+ occurred in 31.5% (median onset 19.9 weeks) 7% pts abandoned cetuximab treatment due to toxicity.

Conclusion

Our data reveal encouraging improvements in skin reactions and their time to occurrence due to a pre-defined skin care.

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Acknowledgements

Merck KGaA provided a medical grant to the University Medicine Mainz to perform the trial, which is registered in the European Union Clinical Trials Register (EudraCT) under the Number 2010-019885-10.

Author information

Authors and Affiliations

  1. Medizinische Klinik II, Klinikum Darmstadt GmbH, Grafenstraße 9, 64283, Darmstadt, Germany

    Carl Christoph Schimanski & Frank Staib

  2. Onkologische Gemeinschaftspraxis Dörfel/Göhler, Leipziger Str. 118, 01127, Dresden, Germany

    Thomas Göhler

  3. Klinikum Schwäbisch Gmünd/Stauferklinik, Wetzgauer Straße 85, 73557, Mutlangen, Germany

    Holger Hebart

  4. Klinikum Dortmund GmbH, Hohe Straße 31, 44137, Dortmund, Germany

    Michael Heike

  5. Onkologische Gemeinschaftspraxis Dr. M. Neise & Dr. A. Lollert, Marktstraße 186, 47798, Krefeld, Germany

    Michael Neise

  6. Theresienkrankenhaus, Bassermannstraße 1, 68165, Mannheim, Germany

    Jochen Rudi

  7. Diakoniekrankenhaus Schwäbisch Hall, Diakoniestraße 10, 74523, Schwäbisch Hall, Germany

    Thomas Geer

  8. Onkologische Schwerpunktpraxis Darmstadt, Eschollbrücker Str. 26, 64295, Darmstadt, Germany

    Gerrit Dingeldein

  9. Kliniken der Stadt Köln GmbH, 51058, Köln, Germany

    Claudia Lang

  10. Praxis für Hämatologie und Onkologie Dr. Ehscheidt, Willi-Brückner-Str. 1, 56564, Neuwied, Germany

    Peter Ehscheidt

  11. Internistische Schwerpunktpraxis Hämatologie/Onkologie, Wallstraße 3-5, 55122, Mainz, Germany

    Thomas Flohr

  12. Gemeinschaftspraxis Hämatologie/Onkologie a. d. Dt. Klinik für Diagnostik GmbH, Aukammallee 33, 65191, Wiesbaden, Germany

    Klaus Maria Josten

  13. Städtisches Klinikum München GmbH Klinikum Neuperlach, Oskar-Maria-Graf-Ring 51, 81737, München, Germany

    Meinolf Karthaus

  14. MVZ Ärzteforum Seestraße, Seestraße 64, 13347, Berlin, Germany

    Alexander Schmittel

  15. Onkologische Schwerpunktpraxis, Speersort 8 3OG, 20095, Hamburg, Germany

    Jan Wierecky

  16. iOMEDICO Clinical Research, Hanferstr. 28, 79108, Freiburg, Germany

    Carl Christoph Schimanski, Emil Boller & Martin Indorf

  17. 1. Med. Klinik, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Germany

    Marcus-Alexander Wörns, Peter R. Galle & Markus Moehler

Authors
  1. Carl Christoph Schimanski
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  2. Frank Staib
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  3. Thomas Göhler
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  4. Holger Hebart
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  5. Michael Heike
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  6. Michael Neise
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  7. Jochen Rudi
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  8. Thomas Geer
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  9. Gerrit Dingeldein
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  10. Claudia Lang
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  11. Peter Ehscheidt
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  13. Klaus Maria Josten
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  14. Meinolf Karthaus
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  15. Alexander Schmittel
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  16. Jan Wierecky
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  17. Emil Boller
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  18. Martin Indorf
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  19. Marcus-Alexander Wörns
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  20. Peter R. Galle
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  21. Markus Moehler
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Corresponding author

Correspondence to Carl Christoph Schimanski.

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Conflict of interest

Carl Christoph Schimanski is acting as an advisory board member for Merck KGaA. Carl Christoph Schimanski has previously received travel support and support for clinical studies from Merck KGaA. The remaining authors declare no conflicts of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

C. C. Schimanski and F. Staib contributed equally to the study.

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Schimanski, C.C., Staib, F., Göhler, T. et al. Dermatux: phase IV trial of Cetuximab plus FOLFIRI in first-line metastatic colorectal cancer receiving a pre-defined skin care. J Cancer Res Clin Oncol 143, 1023–1034 (2017). https://doi.org/10.1007/s00432-017-2344-3

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  • DOI: https://doi.org/10.1007/s00432-017-2344-3

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