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

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.

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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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Keywords

  • Metastatic colorectal cancer
  • Cetuximab
  • Phase IV trial
  • Vitamin K1 ointment
  • Doxycycline
  • Rash
  • Pre-defined skin care