Pinta, F., Ponzetti, A., Spadi, R., Fanchini, L., Zanini, M., Mecca, C., ... Racca, P. (2013). Pilot clinical trial on the efficacy of prophylactic use of vitamin K-based cream (Vigorskin) to prevent cetuximab-induced skin rash in patients with metastatic colorectal cancer. Clinical Colorectal Cancer, 13, 62–67. 

DOI Link

Study Purpose

To determine the efficacy of topical vitamin K1 as prophylaxis for cetuximab-induced skin rash (CISR) in patients with metastatic colorectal cancer

Intervention Characteristics/Basic Study Process

A. Distribution of vitamin K1-based cream (Vigorskin) to subjects occurred before starting cetuximab. The Vigorskin cream contained 0.1% vitamin K1 (phytomenadione), urea, triticum vulgare germ oil, hydrolyzed wheat protein, ceramides-1, -3, and -6 II, and phytosphingosine.     
 
B. Patient education occurred before the initial dose of cetuximab. Teaching included how to correctly use Vigorskin cream (e.g., apply twice daily in morning and before bedtime on face and trunk after washing/taking a bath and after shaving) and general measures on how to minimize CISR (e.g., limit use of hot water and avoid concomitant application of creams containing alcohol or creams for CISR prophylaxis). 
 
C. Management of skin rash occurred according to the proposed protocol by Pinto et al. (2011). If a subject developed grades 3–4 toxicity, then either cetuximab therapy was interrupted, dose was reduced, or therapy was discontinued per study protocol. Patients with grades 3–4 skin rash were referred to a dermatologist.   
 
Data were collected weekly. Investigators paid special attention to the degree of symptoms at weeks 4 and 8. The investigators were adequately trained for assessing skin toxicities and for using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) v3.0.  

Sample Characteristics

  • N = 41
  • MEAN AGE =  67.2 years (SD = 8.2 years)
  • MALES: 25 (61%), FEMALES: 16 (39%)
  • KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer (mCRC)
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients were receiving cetuximab with or without chemotherapy. 61% of patients had a single metastatic site (mostly in the liver). Cetuximab was the first- or second-line treatment in nearly 73% of patients mainly in association with irinotecan; only one patient had a relevant skin comorbidity (e.g., previous temporal herpes zoster). 

Setting

  • SITE: Single-site  
  • SETTING TYPE: Outpatient  
  • LOCATION: Turin, Italy

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Prospective, single cohort study design

Measurement Instruments/Methods

  • The investigators collected demographic data, the degree of disease extension, and occurrence and assessment data regarding the degree of cetuximab-induced skin reactions (CISR) including rash, xerosis, paronychia, and nail and hair changes.
  • National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) v3.0

Results

Overall, 34 patients (82.9%) experienced CISR of any grade. During the first eight weeks of treatment, the grade and incidence of patients’ skin toxicity was grade 0 (6 patients, 15%); grade 1 (18 patients, 45%); grade 2 (10 patients, 25%); and grade 3 (6 patients, 15%). No grade 4 CISR was reported. The mean time to development of the maximum grade of rash was 34.7 days, and the median time was 28 days (SD = 24.7). All patients with grades 2–3 rashes were managed with topical or systemic antibiotics. Dermatologic consultation was provided to all six patients with grade 3 rash.

Conclusions

Overall, this study found that patients with mCRC who were treated with cetuximab and used vitamin K1-based cream prophylactically experienced a lower proportion of grade 2 rash (25%) and grade 3 rash (15%), which corresponds to the lower limit reported in the literature. Also, patients tolerated this treatment well.

Limitations

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Risk of bias (sample characteristics)
  • Findings not generalizable
  • Other limitations/explanation: Study involved only one disease type: mCRC. Forty-one consecutive patients were enrolled. No control.

Nursing Implications

The topical application of vitamin K1-based cream may reduce the risk of developing skin rashes to the lower limits of rash reported elsewhere in the literature. Prophylactic use of vitamin K1 cream is tolerated well by patients receiving cetuximab therapy.