Chemotherapy and Molecular Targeted Therapy

Introduction

Salivary gland carcinomas represent a rare group of malignancies, accounting for 6–8% of all head and neck cancers, and can involve the major or minor salivary glands. According to the World Health Organization (WHO) classification, there are 24 subtypes of salivary gland carcinomas, whose behavior and clinical course vary based on site of origin and histology. The two major categories of salivary gland carcinomas include tumors arising from the intercalated duct, which tend to be lower grade and more indolent, including adenoid cystic carcinoma (ACC), adenocarcinoma, acinic cell carcinoma, myoepithelial carcinoma, and tumors arising from the secretory duct, including salivary duct carcinoma and mucoepidermoid carcinoma (MEC).

Local and Locoregional Disease

The definitive treatment for resectable disease is complete surgical resection. Any adjuvant therapy is reserved for patients with a higher risk of recurrence based on stage, histology, and grade, with radiation therapy (RT) being the primary modality of adjuvant treatments. Evidence for the role of chemoradiotherapy (CRT) has been limited to single institution retrospective studies, and studies have not shown any efficacy of CRT over RT alone. Furthermore, in a review comparing outcomes of patients who received either CRT or RT alone, 2210 patients from the National Cancer Data Base showed a trend toward worsening 2- and 5-year overall survival in patients who received CRT. RTOG-1008 is a prospective ongoing trial evaluating adjuvant RT with or without chemotherapy in high-risk salivary gland tumors.

Recurrent and Metastatic Disease

The most common sites of distant metastases include lymph nodes, lung, liver, and bone. Incidence of metastasis is higher, as expected, in high-grade tumors, with high-grade salivary duct carcinomas developing metastatic disease in ~46% of cases and ACC developing metastases in 25–55% of cases. Local therapy options for limited recurrent disease or carefully selected oligometastatic disease include surgical resection or reirradiation if possible. ACC is notable for its prolonged indolent course, with a median time of 33 months between diagnosis of metastatic disease and death. In such cases, treatment is usually limited to symptomatic disease. Potential treatments may be limited by prior treatment modalities, however, and if local treatment is not possible or the patient develops distant metastases, palliative systemic treatment, including chemotherapy and molecularly targeted therapies, can be considered.

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