Carl Christoph Schimanski1,2, Frank Staib3, Thomas Göhler4, Holger Hebart5, Michael Heike6, Michael Neise7, Jochen Rudi8, Thomas Geer9, Gerrit Dingeldein10, Claudia Lang11, Peter Ehscheidt12, Thomas Flohr13, Klaus Maria Josten14, Meinolf Karthaus15, Alexander Schmittel16, Jan Wierecky17, Emil Boller18, Martin Indorf18, Marcus-Alexander Wörns19, Peter R Galle19, Markus Moehler19. 1. Medizinische Klinik II, Klinikum Darmstadt GmbH, Grafenstraße 9, 64283, Darmstadt, Germany. Carl.Schimanski@mail.klinikum-darmstadt.de. 2. iOMEDICO Clinical Research, Hanferstr. 28, 79108, Freiburg, Germany. Carl.Schimanski@mail.klinikum-darmstadt.de. 3. Medizinische Klinik II, Klinikum Darmstadt GmbH, Grafenstraße 9, 64283, Darmstadt, Germany. 4. Onkologische Gemeinschaftspraxis Dörfel/Göhler, Leipziger Str. 118, 01127, Dresden, Germany. 5. Klinikum Schwäbisch Gmünd/Stauferklinik, Wetzgauer Straße 85, 73557, Mutlangen, Germany. 6. Klinikum Dortmund GmbH, Hohe Straße 31, 44137, Dortmund, Germany. 7. Onkologische Gemeinschaftspraxis Dr. M. Neise & Dr. A. Lollert, Marktstraße 186, 47798, Krefeld, Germany. 8. Theresienkrankenhaus, Bassermannstraße 1, 68165, Mannheim, Germany. 9. Diakoniekrankenhaus Schwäbisch Hall, Diakoniestraße 10, 74523, Schwäbisch Hall, Germany. 10. Onkologische Schwerpunktpraxis Darmstadt, Eschollbrücker Str. 26, 64295, Darmstadt, Germany. 11. Kliniken der Stadt Köln GmbH, 51058, Köln, Germany. 12. Praxis für Hämatologie und Onkologie Dr. Ehscheidt, Willi-Brückner-Str. 1, 56564, Neuwied, Germany. 13. Internistische Schwerpunktpraxis Hämatologie/Onkologie, Wallstraße 3-5, 55122, Mainz, Germany. 14. Gemeinschaftspraxis Hämatologie/Onkologie a. d. Dt. Klinik für Diagnostik GmbH, Aukammallee 33, 65191, Wiesbaden, Germany. 15. Städtisches Klinikum München GmbH Klinikum Neuperlach, Oskar-Maria-Graf-Ring 51, 81737, München, Germany. 16. MVZ Ärzteforum Seestraße, Seestraße 64, 13347, Berlin, Germany. 17. Onkologische Schwerpunktpraxis, Speersort 8 3OG, 20095, Hamburg, Germany. 18. iOMEDICO Clinical Research, Hanferstr. 28, 79108, Freiburg, Germany. 19. 1. Med. Klinik, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
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.
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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Authors: Thomas C Wehler; Claudine Graf; Markus Möhler; Jutta Herzog; Martin R Berger; Ines Gockel; Hauke Lang; Matthias Theobald; Peter R Galle; Carl C Schimanski Journal: J Cancer Res Clin Oncol Date: 2013-08-07 Impact factor: 4.553