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Clinical Trial
. 2017 Jun;143(6):1023-1034.
doi: 10.1007/s00432-017-2344-3. Epub 2017 Feb 14.

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

Carl Christoph Schimanski  1   2 , Frank Staib  3 , Thomas Göhler  4 , Holger Hebart  5 , Michael Heike  6 , Michael Neise  7 , Jochen Rudi  8 , Thomas Geer  9 , Gerrit Dingeldein  10 , Claudia Lang  11 , Peter Ehscheidt  12 , Thomas Flohr  13 , Klaus Maria Josten  14 , Meinolf Karthaus  15 , Alexander Schmittel  16 , Jan Wierecky  17 , Emil Boller  18 , Martin Indorf  18 , Marcus-Alexander Wörns  19 , Peter R Galle  19 , Markus Moehler  19
Affiliations
Clinical Trial

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

Carl Christoph Schimanski et al. J Cancer Res Clin Oncol. 2017 Jun.

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.

Keywords: Cetuximab; Doxycycline; Metastatic colorectal cancer; Phase IV trial; Pre-defined skin care; Rash; Vitamin K1 ointment.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates of overall survival (OS) and progression-free survival (PFS) of the modified intend to treat (mITT) population. a shows progression-free survival among the 54 patients in the mITT population (number of events: 14/54; 25.9%). Median progression-free survival time was 8.5 months (95% CI 7.7–11.2). b shows preliminary overall survival time among the 54 patients in the mITT population (number of events: 26/54; 48.1%). The data are preliminary as there are still patients in the OS follow-up. Median overall survival time was 21.8 months (95% CI 16.8–29.7)
Fig. 2
Fig. 2
Cox regression analysis of overall survival (OS) of the modified intend to treat (mITT) population (forest plot)
See this image and copyright information in PMC

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