Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland

Abstract

Adenoid cystic carcinoma (ACC) is the most common malignant epithelial cancer of the lacrimal gland. Despite a slow rate of growth, ACCs are ultimately associated with poor clinical outcome. Given the rarity of this disease, most recommendations regarding therapy are guided by expert opinion and retrospective data rather than level 1 evidence. Surgery and postoperative radiation therapy are commonly used as initial local treatment. In patients at high risk of recurrence, concomitant platinum-based chemotherapy may be added to postoperative radiotherapy in an attempt to enhance radio-sensitivity. While encouraging responses have been reported with intra-arterial neoadjuvant chemotherapy, this strategy is associated with substantial toxicity and should be considered investigational. For patients with metastatic disease not amenable to surgery or radiotherapy, chemotherapy may have a role based on its modest efficacy in non-lacrimal ACC. Similarly, molecular targeted agents may have a role, although the agents tested to date in non-lacrimal ACC have been disappointing. A better understanding of the biology of ACC will be crucial to the future success of developing targeted agents for this disease.

Adenoid cystic carcinoma of the lacrimal gland: role of nuclear survivin (BIRC5) as a prognostic marker

“…The primary treatment for ACC of the lacrimal gland has been en‐bloc surgical excision, which is usually followed by postoperative radiotherapy . Neoadjuvant chemotherapy carries a risk of substantial toxicity …”

“…11,12 Neoadjuvant chemotherapy carries a risk of substantial toxicity. 13 Cytotoxic agents have been associated with dismal antitumour activity in metastatic ACC of the salivary glands; this uniform lack of efficacy has prompted the evaluation of molecularly targeted therapies in these tumours. Unfortunately, their theoretical promise has yet to be fulfilled.…”

Adenoid cystic carcinoma of the head and neck

“…Regardless, the noted duration of response with these traditional chemotherapy approaches has been reportedly short in a majority of cases—usually 5 to 13 months 5, 17‐19. The use of intra‐arterial chemotherapy has been disappointing 20…”

“…One such class of targeted agents includes the c‐KIT inhibitor. c‐KIT has a high expression rate in ACC, ranging from 78% to 100% 20, 23, 24. A better understanding of the biology and molecular pathogenesis of ACC will be crucial to the future success of targeted agents for this disease.…”

Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial

“…More recently, targeted therapies are expected to improve the efficacy of treatment. Unfortunately, their theoretical promise has yet to be fulfilled (Le Tourneau et al , 2011). In view of frequent epidermal growth factor receptor (EGFR) positivity in ACC (74–91%) (Vered et al , 2002; Agulnik et al , 2007; Macarenco et al , 2008; Dahse et al , 2009; Locati et al , 2009a), the EGFR antibody cetuximab seemed promising.…”