imatinib can inhibit c-kit, platelet-derived growth factor receptor, and EGFR.

A few attempts have been made to use imatinib for treatment of orbital and periocular tumors. Vigna and associates [31] reported a case of an orbital mass due to chronic eosinophilic leukemia successfully treated with imatinib. A study of six orbital lymphangiomas showed platelet-derived growth factor receptor expression in the endothelium of all six and EGFR expression in five of six [13]. Although the expression of these two receptors suggests that these tumors might be sensitive to imatinib, preliminary studies have shown a questionable response (B. Esmaeli, 2004).

Adverse e ects associated with the use of imatinib include nausea, myalgias, edema, diarrhea, fatigue, rash, dyspepsia, vomiting, thrombocytopenia, neutropenia, and arthralgias [9]. Edema is the most commonly seen adverse e ect, and the periorbital region is the most common site for edema [7, 34]. In a phase I trial of imatinib for the treatment of gastrointestinal stromal tumor, edema of the periorbital region or eyelids was seen in 55.1% of the 174 patients treated [6]. Rarely, the edema can be so severe that surgical treatment is required [12]

13.5Cetuximab

Cetuximab is a monoclonal antibody directed against EGFR, a member of the ErbB family of tyrosine kinase receptors. EGFR is involved in the pathogenesis and progression of certain cancers [22]. Cetuximab is used in the treatment of colon cancer and head and neck SCC [17]. Although SCC in the head and neck can involve the orbit, we found no published reports of cetuximab used in the treatment of periorbital SCC at the time of preparation of this chapter.

Shepler and associates [26] evaluated EGFR expression in conjunctival SCC. They found EGFR expression in five of five specimens, suggesting that inhibitors of EGFR may be useful in patients with SCC [26]. Ivan and associates [19] found EGFR expression in both ocular and extraocular sebaceous gland carcinomas, again suggesting a potential role for EGFR inhibitors in treatment of sebaceous gland carcinoma of eyelid.

In addition to cetuximab, a number of other EGFR inhibitors are currently available, including lapatinib, panitumumab, erlotinib, and gefitinib. Potential periocular side e ects of EGFR inhibitors include trichomegaly (Fig. 13.4), blepharitis, and acneiform rash [1, 30].

13.5 Cetuximab 191

Fig. 13.4 An example of trichomegaly in a patient with lung carcinoma treated with erlotinib. This patient needs periodic trimming of his eyelashes to prevent visual obstruction by long and misdirected eyelashes

Summary for the Clinician

Targeted therapies have already become part of the standard therapy for certain malignancies. A multitude of new targeted agents are under investigation. As new cellular markers are identified and additional targeted therapies become available, there will be an increasing role for targeted therapies in the treatment of periocular tumors.

■A number of targeted therapies have become part of the standard therapy for certain malignancies, and we are beginning to gain insights about their use for orbital and periorbital diseases.

■The use of rituximab for benign lymphoid hyperplasia of the orbit is intriguing. Rituximab can also be used for treatment of low-grade lymphomas of the orbit and ocular adnexa but is more e ective and associated with a lower risk of relapse when it is used in combination with other drugs or treatment modalities.

■EGFR expression in conjunctival SCC and sebaceous gland carcinoma may suggest a potential role for a number of EGFR inhibitors for treatment of these cancers, but to date this has not been clinically tried.

■Common ocular side e ects of new targeted therapies include periorbital edema for imatinib mesylate and trichomegaly associated with EGFR inhibitors.

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