Skip to main content
SpringerLink
Log in

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

Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Cite this article

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27(5):663–671

    Article  CAS  PubMed  Google Scholar 

  • Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345

    Article  CAS  PubMed  Google Scholar 

  • Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmuller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Muller S, Link H, Niederle N, Rost A, Hoffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 15(10):1065–1075

    Article  CAS  PubMed  Google Scholar 

  • Janus N, Launay-Vacher V, Robert C, Souquet PJ, Mateus C, Dreno B, Deray G, Morere JF, Deplanque G (2009) Description of erlotinib-related skin effects management in France. Results of the PRECEDE study. Cancer Radiother 13(2):97–102

    Article  CAS  PubMed  Google Scholar 

  • Jatoi A, Rowland K, Sloan JA, Gross HM, Fishkin PA, Kahanic SP, Novotny PJ, Schaefer PL, Johnson DB, Tschetter LK, Loprinzi CL (2008) Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: results of a placebo-controlled trial from the North Central Cancer Treatment Group (N03CB). Cancer 113(4):847–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karashima T, Sweeney P, Slaton JW, Kim SJ, Kedar D, Izawa JI, Fan Z, Pettaway C, Hicklin DJ, Shuin T, Dinney CP (2002) Inhibition of angiogenesis by the antiepidermal growth factor receptor antibody ImClone C225 in androgen-independent prostate cancer growing orthotopically in nude mice. Clin Cancer Res 8(5):1253–1264

    CAS  PubMed  Google Scholar 

  • Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti N, Xu F, Yassine M (2010) Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol 28(8):1351–1357

    Article  CAS  PubMed  Google Scholar 

  • O’Dwyer PJ, Benson AB, 3rd (2002) Epidermal growth factor receptor-targeted therapy in colorectal cancer. Semin Oncol 29(5 Suppl 14): 10–17

    Article  PubMed  Google Scholar 

  • Ocvirk J (2010) Management of cetuximab-induced skin toxicity with the prophylactic use of topical vitamin K1 cream. Radiol Oncol 44(4):265–266

    Article  PubMed  PubMed Central  Google Scholar 

  • Ocvirk J, Cencelj S (2010) Management of cutaneous side-effects of cetuximab therapy in patients with metastatic colorectal cancer. J Eur Acad Dermatol Venereol 24(4):453–459

    Article  CAS  PubMed  Google Scholar 

  • Pinta F, Ponzetti A, Spadi R, Fanchini L, Zanini M, Mecca C, Sonetto C, Ciuffreda L, Racca P (2014) Pilot clinical trial on the efficacy of prophylactic use of vitamin K1-based cream (Vigorskin) to prevent cetuximab-induced skin rash in patients with metastatic colorectal cancer. Clin Colorectal Cancer 13(1):62–67

    Article  CAS  PubMed  Google Scholar 

  • Racca P, Fanchini L, Caliendo V, Ritorto G, Evangelista W, Volpatto R, Milanesi E, Ciorba A, Paris M, Facilissimo I, Macripo G, Clerico M, Ciuffreda L (2008) Efficacy and skin toxicity management with cetuximab in metastatic colorectal cancer: outcomes from an oncologic/dermatologic cooperation. Clin Colorectal Cancer 7(1):48–54

    Article  CAS  PubMed  Google Scholar 

  • Roe E, Garcia Muret MP, Marcuello E, Capdevila J, Pallares C, Alomar A (2006) Description and management of cutaneous side effects during cetuximab or erlotinib treatments: a prospective study of 30 patients. J Am Acad Dermatol 55(3):429–437

    Article  PubMed  Google Scholar 

  • Schimanski CC, Moehler M, Zimmermann T, Worns MA, Steinbach A, Baum M, Galle PR (2010) Cetuximab-induced skin exanthema: improvement by a reactive skin therapy. Mol Med Rep 3(5):789–793

    CAS  PubMed  Google Scholar 

  • Scope A, Agero AL, Dusza SW, Myskowski PL, Lieb JA, Saltz L, Kemeny NE, Halpern AC (2007) Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol 25(34):5390–5396

    Article  CAS  PubMed  Google Scholar 

  • Stintzing S, Kapaun C, Laubender RP, Jung A, Neumann J, Modest DP, Giessen C, Moosmann N, Wollenberg A, Kirchner T, Heinemann V (2013) Prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: results from a randomized trial of the GERMAN AIO CRC Study Group. Int J Cancer 132(1):236–245

    Article  CAS  PubMed  Google Scholar 

  • Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P (2009a) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360(14):1408–1417

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, Topham C, Tabernero J, Andre T, Sobrero AF, Mini E, Greil R, Di Costanzo F, Collette L, Cisar L, Zhang X, Khayat D, Bokemeyer C, Roth AD, Cunningham D (2009b) Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol 27(19):3117–3125

    Article  PubMed  Google Scholar 

  • Vanhoefer U (2003) Novel molecular approaches in the therapy of advanced colorectal carcinoma. Onkologie 26(Suppl 7): 70–74

    CAS  PubMed  Google Scholar 

  • Wehler TC, Graf C, Mohler M, Herzog J, Berger MR, Gockel I, Lang H, Theobald M, Galle PR, Schimanski CC (2013) Cetuximab-induced skin exanthema: prophylactic and reactive skin therapy are equally effective. J Cancer Res Clin Oncol 139(10):1667–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank Staib
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Göhler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Holger Hebart
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Heike
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael Neise
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jochen Rudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thomas Geer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gerrit Dingeldein
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Claudia Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Peter Ehscheidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Thomas Flohr
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Klaus Maria Josten
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Meinolf Karthaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Alexander Schmittel
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jan Wierecky
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Emil Boller
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Martin Indorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Marcus-Alexander Wörns
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Peter R. Galle
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Markus Moehler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carl Christoph Schimanski.

Ethics declarations

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.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

search

Navigation