Subcutaneous abscess as a side-effect of cetuximab therapy

ARTICLE

ejd.2010.1231

Auteur(s) : Cristina GUERRIERO¹, Francesco RICCI¹, Andrea PARADISI¹, Barbara FOSSATI¹, Vincenzo VALENTINI², Fabio PACELLI³, Rodolfo CAPIZZI¹ fraric1984@libero.it

¹ Department of Dermatology,

² Department of Radiotherapy,

³ Department of Digestive Surgery, Catholic University of the Sacred Heart, L.go A Gemelli 8 - 00168 Rome, Italy

Cetuximab, a chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), is used to treat colorectal cancer and head and neck squamous-cell carcinoma (SCC) [2]. Common adverse events associated with cetuximab treatment are paronychia, diarrhea, and nausea, but most frequently acneiform eruption (>90%, with 20% grade 3/4 severity) [1].

A 68-year-old man with tonsil SCC (cT4aN1Mo according to the TNM classification) underwent radio-chemotherapy with cetuximab and hyperfractionated radiotherapy. Cetuximab was infused intravenously according to the traditional protocol, which consists of a loading dose of 400/m² (total dose 780 mg) over 2 h, followed by 250/m² (total dose 485-585 mg) weekly for 7 weeks.

Dermatological examination showed grade 3 skin and mucous membrane toxicities (according to the National Cancer Institute–CTCAE criteria) [2] with confluent oral pseudomembranous ulcers, widespread folliculitis with erythema on the face and upper trunk, and bleeding induced by minor trauma.

At the end of the 7^th cycle, a tight, erythematous, painful abscess, 9-10 cm in diameter, arose on the patient's right buttock (figure 1). There was no fever, the patient was not diabetic nor immunocompromised, and all laboratory parameters were within normal ranges. Oral clarithromycin 1 g daily and chlorphenamine maleate 8 mg daily for 5 days did not result in significant improvement. Surgical drainage of the abscess on the 6^th day yielded a culture positive for Staphylococcus aureus.

The response to cetuximab treatment was initially good, with a marked reduction of the primary tumor and involved lymph nodes on the imaging studies. However, a year after chemotherapy, the patient required further surgery due to tumor spread to other lymph nodes and the sphenoid sinus.

The EGFR family of receptor tyrosine kinases is at the beginning of a complex signal cascade that modulates cell proliferation, differentiation, migration and survival. It is overexpressed in several epithelial neoplasms, including head and neck SCC, non-small-cell lung, colon, prostate, ovarian and kidney cancers. EGFR blockade by target monoclonal antibodies (such as cetuximab) represents a novel strategy for cancer treatment.

Skin reactions associated with cetuximab are acne-like rash, cutaneous xerosis, paronychia, telangiectasia, itch, xerophthalmia, eyelash trichomegaly and residual hyperpigmentation. Acneiform rash is the commonest adverse event, with a characteristic distribution in seborrheic areas (face, V-shaped neckline, upper trunk). The skin lesions sometimes consist of erythematous follicular papules that may evolve into pustules. The pathogenesis of acneiform rash is unclear. EGF family receptors play important roles in protecting the hair follicle from immunomediated damage and in permitting the transition of hair and vellus hairs from the growth (anagen) to the involution phase (catagen). Consequently, EGFR inhibition keeps vellus hairs in the catagen phase for a long time, resulting in follicle damage. Abscess formation in our patient was probably due to a combination of cetuximab-induced folliculitis and S. aureus superinfection.

There is no standard treatment for the rash induced by EGFR-inhibitors, and there are different views on antibiotic prophylaxis in patients receiving cetuximab [1]. Its effectiveness has not been proven because the cause of the acneiform eruption is initially inflammatory, but is then frequently followed by superinfection. Moreover, the contradictory results of the few relevant trials [3, 4] do not warrant routine use of this approach. A recent uncontrolled open label follow-up study [5] reported a significant improvement of cetuximab-induced acneiform eruptions by topical therapy with nadifloxacin cream and prednicarbate cream. In another study [6], grades equal to or higher than the second were successfully treated with oral tetracyclines. However, no controlled studies on the interference between systemic therapy and tumor response to EGFR inhibitors are currently under way.

In our patient antibiotic prophylaxis would probably have prevented abscess formation, improving his condition and enabling a better management.

Disclosure

Financial support: none. Conflict of interest: none.

Reference

1 J Bernier, J Bonner, JB Vermorken et al. Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck Ann Oncol 2008; 19: 142-149.

2 Anon C. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). http://clep.cancer.gov/forms/CTCAEv3.pdf.

3 A Jatoi, K Rowland, JA Sloan et al. Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes Cancer 2008; 113: 847-853.

4 A Scope, ALC Agero, SW Dusza 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.

5 K Katzer, J Tietze, E Klein 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: 82-84.

6 NM Menezes, R Lima, A Moreira et al. Description and management of cutaneous side effects during erlotinib and cetuximab treatment in lung and colorectal cancer patients: a prospective and descriptive study of 19 patients Eur J Dermatol 2009; 19: 248-251.