Wehler, T.C., Graf, C., Mohler, M., Herzog, J., Berger, M.R., Gockel, I., ... Schimanski, C.C. (2013). Cetuximab-induced skin exanthema: Prophylactic and reactive skin therapy are equally effective. Journal of Cancer Research and Clinical Oncology, 139(10), 1667–1672. 

DOI Link

Study Purpose

To determine the effectiveness of several treatment options in decreasing cetuximab-induced skin exanthema in three study populations: the historic group (no standard skin treatment); the proactive skin therapy group; and the reactive skin therapy group

Intervention Characteristics/Basic Study Process

Group A (historic cohort, n = 20) did not receive skin prophylaxis or reactive skin treatment.  
 
Group B (reactive skin therapy cohort, n =`15) received the following reactive skin protocol after an exanthema developed. Grade 1 exanthema: topical cleansing syndet and topical metronidazole 7.5% cream on affected areas. Grade 2 exanthema: grade 1 treatment and oral minocycline 50 mg BID. Grade 3 exanthema: Grade 2 treatment and topical corticoid prednicarbat cream (0.25%) on affected areas. 
 
Group C (proactive skin therapy cohort, n = 15) began a skin prophylaxis regimen with the first cetuximab dose. This included the application of a topical cleansing syndet, a topical metronidazole ointment (7.5%), and oral doxycycline 100 mg BID. If grades 3–4 exanthema developed, topical corticoid prednicarbat cream (0.25%) was applied. If grades 3–4 rash developed, the reactive skin protocol was initiated.
 
Data were gathered weekly. 

Sample Characteristics

  • N = 50
  • AGE = Not reported
  • MALES: Not reported, FEMALES: Not reported
  • KEY DISEASE CHARACTERISTICS: Gastrointestinal adenocarcinoma, Union for International Cancer Control (UICC) stage 4 
  • OTHER KEY SAMPLE CHARACTERISTICS: All patients had a history of receiving chemotherapy (either FOLFIRI or FOLFOX) in combination with a standard dosing of cetuximab (initially 400 mg/m2 and thereafter 250 mg/m2 weekly). None of the patients received radiation therapy. None of the patients had a history of acne. The patient decided whether he or she would receive the reactive therapy or the prophylactic therapy. 

Setting

  • SITE: Multi-site  
  • SETTING TYPE: Not specified  
  • LOCATION: Several cities (Mainz, Darmstadt, and Heidelberg) in Germany

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment
  • APPLICATIONS: Palliative care 

Study Design

Retrospective analysis

Measurement Instruments/Methods

  • National Cancer Institute Common Terminology Criteria for Adverse Events (NCI, CTCAE) v3.0 criteria
  • Physical exam
  • Digital photography

Results

  • In comparing time to onset of ≥ grade 2 exanthema, all three groups were at one to four weeks. Average time to onset was 14.7 days for group A, 13.2 days for group B, and 13.9 days for croup C.  
  • In comparing maximum exanthema (grades 0–I versus 2, 3, and 4), results showed a significant difference between groups A and B (p = 0.027) and between groups A and C (p = 0.069). However, there existed no significant differences between groups B and C (p = 0.69).  
  • In comparing frequency of therapy interruption, group C (historic cohort) showed a frequency of 40% discontinuation of cetuximab therapy compared to 0% in group A and 7% (n = 1) in group B. 

Conclusions

Using this simple reactive skin protocol can prevent the exacerbation of cetuximab-induced follicular exanthema. This therapy can stabilize exanthema development. Results of the prophylactic skin treatment cohort showed equally effective, but not superior, results in preventing skin toxicity ≥ grade 2. Both groups B and C had lower therapy interruptions.

Limitations

  • Small sample (< 100)
  • Risk of bias (no blinding)
  • Risk of bias (sample characteristics)
  • Findings not generalizable
  • Other limitations/explanation: Sample characteristics were not identified (e.g., male, female, age). The algorithm for the prophylactic skin protocol on page 1,669 did not match the protocol described in the text (e.g., the algorithm included vitamin K1, which was never discussed in the text). The algorithm had cleansing syndet and topical metronidazole in the row of grade 2, but this info should have been in the box for grades 0–1. Likewise, vitamin K1 and minocycline should not have been in the grades 0–1 box.

Nursing Implications

Nurses need to assess for exanthema, which generally develops within one to four weeks of initiating cetuximab. Prophylactic and reactive skin protocols are equally effective and may be easier to handle in practice. Both prophylactic and reactive skin treatments reduce higher grades of exanthema, which can lead to therapy cessation.