Case ReportTreatment of squamous cell vulvar cancer with the anti-EGFR tyrosine kinase inhibitor Tarceva
Introduction
Vulvar cancer is the fourth most common female genital tract malignancy following cancers of the uterine corpus, ovary and cervix. In 2006, 3740 new cases and 880 deaths were reported from this disease in the United States alone [1]. The standard treatments of vulvar cancer are surgical excision, inguino-femoral lymphadenectomy when appropriate and/or radiation therapy with or without concurrent chemotherapy for locally advanced disease. Though often successful, treatments are associated with significant morbidity. Several lines of evidence have shown that primary vulvar cancers as well as metastatic lesions have increased expression of the epidermal growth factor receptor (EGFR) [2], [3]. EGFR is a 170-kDa transmembrane receptor that has tyrosine kinase activity. It is closely related to three other receptor tyrosine kinases making up the ErbB family. Transcribed from chromosome 7p12, this receptor is composed of an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Once ligand binds to the receptor, conformational changes occur and the EGFR molecule dimerizes or heterodimerizes with related ErbB family receptors. Autophosphorylation and trans-phosphorylation ensue which leads to a downstream signaling cascade that results in proliferation, angiogenesis, metastasis, and inhibition of apoptosis. Erlotinib (Tarceva), is a small molecule, orally administered inhibitor of EGFR tyrosine kinase. By competing with ATP for binding to the ATP site in the EGFR tyrosine kinase domain, Tarceva abrogates the receptor's catalytic activity, receptor autophosphorylation, and its engagement with signal transducers. This drug is very well tolerated with diarrhea, rash, and fatigue as its major toxicities. Given the overexpression of EGFR in vulvar cancers the question arises as to whether or not Tarceva may be an effective treatment of vulvar cancer. In this report, we give the details of the first two cases of squamous cell vulvar cancer treated with erlotinib.
Section snippets
Case report 1
A 75 year old lady presented with 4 months history of an exophytic vulvar mass. The 5 cm mass had an ulcer on the surface with occasional bleeding and pain. A biopsy of the mass revealed infiltrating moderately differentiated squamous cell carcinoma. This tumor was at least stage III (involvement of lower urethra). The patient's other medical co-morbidities include hypertension, chronic renal insufficiency, congestive heart failure, atrial fibrillation, and myeloproliferative disorder.
Case report 2
A 60 year old obese woman presented to the general surgery team with two lower anterior abdominal wall abscesses. One lesion measured 9.9 cm and contained a fistulous tract to the mons pubis; the second lesion was a 5.3 cm abscess in the right inguinal region consistent with infected necrotic lymph node tissue. At the time of surgical drainage of these abscesses she was also found to have a 6 cm necrotic left vulvar mass involving the upper half of the left labia majus. Biopsy of this mass
Discussion
Vulvar cancer accounts for 5% of all female genital cancers and 1% of all malignancies in women [4]. The commonest histological type is squamous cell carcinoma of the vulva. Surgical resection remains the mainstay of treatment for this disease. However, surgery is associated with significant complications with an operative mortality of up to 2% and significant morbidities such as lower extremity lymphedema (30 to 70%) and sexual dysfunction with 75% of previously sexually active women reporting
Acknowledgments
Special thanks to Daphne Bell and Dennis Sgroi for performing the correlative studies on the biopsy material.
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