Imatinib for advanced adenoid cystic carcinoma of head and neck. A phase II study

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Introduction: Adenoid cystic carcinoma of the salivary glands is an uncommon tumor characterized by slow growth and poor response to chemotherapy. Most cases of adenoid cystic carcinoma of the salivary glands express the c-kit protein, often with very high levels of expression. Imatinib mesylate (Gleevec) inhibits several protein-tyrosine kinases, including c-Kit and we therefore hypothesized that it may have activity against these tumors. We therefore conducted a phase 2 study of imatinib in patients with locally advanced or metastatic adenoid cystic carcinoma. Materials & Methods: Patients with histologically proven adenoid cystic carcinoma, performance status 0-3 and life expectancy of more than 3 months, who had metastatic disease or who had loco-regional disease which was judged by our head and neck cancer tumor board not to be amenable to curative therapy were eligible for this study. Fourteen eligible patients who consented to participate in the study were screened. Ten patients (71%) had c-kit positive tumors and entered the study. Results: All patients began treatment with a dose of Imatinib of 400 mg/day. The dose of Imatinib was increased to 600 mg/day in three patients and to 800 mg in one patient. Three patients had dose reduction to 300 mg/d, one because of grade 3 diarrhea, one due to fatigue and one patient due to both fatigue and peri-orbital edema. No grade 4 toxicity was seen. No objective responses were seen. Two patients died of progressive disease within 2 months after beginning therapy. One patient with lung metastases had stable disease for 14 months and one patient with extensive maxillary disease was stable for 11 months. All six other patients stopped treatment after 4-14 (median 6) months due to progressive disease. Conclusions: Two patients (20%) exhibited stable disease for 11-14 months. Adenoid cystic carcinoma is a usually a slow growing tumor and stable disease for prolonged periods may be seen without treatment. In our study Imatinib had only a minor effect on advanced adenoid cystic carcinoma of the head and neck.