Jo, J.C., Hong, Y.S., Kim, K.P., Lee, J.L., Kim, H.J., Lee, M.W., ... Kim, T.W. (2013). Topical vitamin K1 may not be effective in preventing acneiform rash during cetuximab treatment in patients with metastatic colorectal cancer. European Journal of Dermatology, 23(1), 77–82. 

To investigate the efficacy and safety of vitamin K1 cream for cetuximab-associated acneiform rash

All participants in the research arm were given vitamin K1 (phytomenadione 0.1%, Reconval^® K1, manufactured by DRODERM^® in Slovenia) before initiating cetuximab therapy. A participant was to apply vitamin K1 to his or her face, anterior, and posterior trunk twice daily on day 1 and throughout therapy. Concomitant oral antibiotics were allowed for grades ≥ 2 acneiform rashes. Evaluation of compliance and observance of rashes took place at each clinic visit. The study population was compared to a historical control group that had received cetuximab-containing chemotherapy with or without oral antibiotics but without topical K1 cream. A dermatologist graded rash severity.

• N = 101
• AVERAGE AGE = 56.5 years
• MALES: 62% in study arm and 75% in control arm, FEMALES: 38% in study arm and 25% in control arm
• KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer with metastases to liver, lymph nodes, peritoneum, and/or lung. All patients were KRAS wild-type. 
• OTHER KEY SAMPLE CHARACTERISTICS: Study arm participants were ECOG 0–1, 93%, (> 2, 7%); control patients were 0–1 ECOG, 100%; no one in the study arm had received an EGFR inhibitor or had received topical or oral treatment for dermatologic reasons.

• SITE: Single-site  
• SETTING TYPE: Not specified  
• LOCATION: Asan Medical Center, Seoul, Korea

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

Non-randomized, open-label, interventional study with historical control

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) v3.0 to grade rash severity

In the historical control, acneiform rash of any grade occurred in 97.5% of patients. In the experimental group, 88.5% of patients experienced any grade of rash. No significant difference was found between the groups. There was no significant difference between groups for the median time to rashes grades ≥ 1 or time to rashes grades ≥ 2. There was no significant difference in the overall occurrence of rashes grades ≥ 2 between the groups at any point. There was no significant difference in the time to improvement from grades ≥ 2 to grades ≥ 1 rashes.

Vitamin K1 is not an effective prophylactic treatment of acneiform rash associated with cetuximab treatment.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Findings not generalizable
• Other limitations/explanation: Data do not support the comparison of results to any other disease sites also using cetuximab therapy. Non-randomized, non-blinded trial.

Nurses should be aware that using topical vitamin K1 for prophylaxis of cetuximab-associated acneiform rash is not an effective treatment. Other interventions should be considered for patients receiving EGFR therapy for the management of acneiform rash.