Cetuximab is one of two approved epidermal growth factor inhibitor (EGFRI) monoclonal antibody agents in the treatment of metastatic colorectal cancer (mCRC). Targeting the EGFR, cetuximab prevents the activation and signal transduction that can lead to tumor cell growth and proliferation. Cetuximab is approved as a single therapy or in conjunction with chemotherapy for patients with mCRC who have wild-type K-ras (versus mutated K-ras in which the drug has no clinical activity).1  Common side effects of cetuximab include the EGFRI-associated rash, which is papular-pustular in appearance, and can appear as a mild, moderate or severe skin eruption.2 Although the rash is often called acneiform, it is not considered acne, and common acne therapies such as oral retinoids are not recommended in this setting. The appearance of the EGFRI-associated rash is linked to a higher response rate and longer survival; in fact, patients with more significant rashes had longer overall survival.3 Rash is therefore desired and yet therapy with EGFRI agents may be interrupted or discontinued if rash is severe. Because of this, clinicians are studying best practices for management of the EGFRI-associated rash. Recent research has shown benefit with the oral systemic semi-synthetic tetracycline agents such as minocycline and doxycycline.4,5 However, antibiotic creams, such as clindamycin, have also been recommended for the treatment of mild to moderate rash.1 

A recently reported trial by Katzer and colleagues6 studied the efficacy of topical therapy with nadifloxacin cream and prednicarbate cream in a small study of 29 patients.

Study Facts  
  • The trial was an uncontrolled, open label follow-up study with 29 oncology patients on cetuximab
  • The participants were diagnosed with various forms of metastatic cancer, including mCRC
  • All patients had clinically and histologically verified mild, moderate or severe acneiform eruptions
  • All patients treated their skin eruptions topically with nadifloxacin 1% cream once daily in the morning in combination with prednicarbate 0.25% cream once daily in the evening for six weeks
  • Other supportive care agents were allowed in all patients, such as sunscreens, cleansers or antihistamines
  • The clinical severity of the rash was recorded using the authors’ severity score for acneiform skin eruptions (Skin-Score) before and after 1, 2,and 6 weeks of topical treatment with  nadifloxacin and prednicarbate

Results
Striking improvement was seen after the first week of therapy, with an additional improvement noted after two and six weeks. The Skin-Score showed a significant reduction between all time points analyzed, and subjective symptoms such as itching, tenderness and discomfort were significantly improved. Almost all pustules and papules were gone after four weeks of therapy with the nadifloxacin and prednicarbate. The topical therapy was well tolerated, with only two patients reporting mild side effects such as burning and erythema and all patients were very satisfied with the new treatment.

The authors also noted: 

  •  The entirely topical treatment approach does not interfere with efficacy of cetuximab and avoids potential drug interactions
  •  Significant improvement occurred within one week, with additional improvement at two and six weeks
  •  Nadifoxacin, an anti-bacterial quinolone derivate is often used as a topical treatment for acne, but has antimicrobial and immunomodulatory effects
  •  Prednicarbate was chosen because of its well-established anti-inflammatory effects and an improved risk-benefit ration

Nursing Implications
Standardization of treatment for EGFRI-associated rash does not exist; however, multiple small trials have shown benefit with various treatment strategies, including oral semi-synthetic tetracycline agents. This trial of 29 patients, although uncontrolled and open-label, shows efficacy with the use of nadrifloxacin and prednicarbate as a topical-only regime. The results add to the current body of knowledge regarding possible treatment strategies for EGFRI-associated rash. As the use of EGFRI agents increases in patients with cancer, optimal management of the side effects, including rash, is necessary. Oncology nurses should be aware of the latest study results for management of EGFRI-associated rash.

References

  1. Burtness B, Anadkat M, Basti S, et al. NCCN Task Force Report: Management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. JNCCN. 2009;7[suppl. 1]:S-1-S24.
  2. Lynch TJ, Kim ES, Eaby B, et al. Epidermal growth factor receptor inhibitor–associated cutaneous toxicities: An evolving paradigm in clinical management. Oncologist. 2007;12:610-621.
  3. Van Cutsem E. Challenges in the use of epidermal growth factor receptor inhibitors in colorectal cancer. Oncologist. 2006;11:1010-1017.
  4. Lacouture ME, Mitchell EP, Shearer H, et al. (2009). Impact of pre-emptive skin toxicity (ST) treatment (tx) on panitumumab (pmab)-related skin toxicities and quality of life (QOL) in patients (pts) with metastatic colorectal cancer (mCRC): Results from STEPP [abstract 291] Presented at 2009 Gastrointestinal Cancers Symposium, ASCO. Retrieved November 30, 2009 from the http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=63&abstractID=10396. 
  5. Scope A, Agero AL, Dusza SW, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25:5390-5396.
  6. Katzer K, Tietzd J, Klein E, et al. Topical therapy with nadifloxacin cream and  prednicarbate cream improves acneiform eruptions caused by the EGFR-inhibitor  cetuximab - A report of 29 patients. Eur J Dermatol. 2010;20:1-3.