Treatment of Advanced Adrenocortical Carcinoma with Erlotinib plus Gemcitabine

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Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. In advanced disease, mitotane given as monotherapy or combined either with etoposide, doxorubicin, and cisplatin or with streptozotocin is the recommended first-line therapy. However, many patients have progressive disease despite treatment with these regimens. Our objective was to evaluate the efficacy of the epidermal growth factor receptor inhibitor erlotinib plus gemcitabine as salvage therapy in ACC patients with very advanced ACC. The study consisted of case series collected from different centers (primary care and referral centers) in Germany in 2006-2007. Patients registered with the German ACC Registry with progressive ACC after two to four previous systemic therapies were offered treatment with erlotinib and gemcitabine. Oral erlotinib (100 mg/d) was administered on a daily basis and gemcitabine (800 mg/m(2)) iv every 14 d. We evaluated tumor response according to response evaluation criteria in solid tumors (RECIST) criteria after 12 wk of treatment. Ten patients have been treated with erlotinib and gemcitabine. Only one in 10 patients experienced a minor response (progression-free survival 8 months), whereas eight patients had progressive disease at the first staging. One patient had to stop therapy after the first administration of gemcitabine due to cerebral seizure. Nine of 10 patients had died after a median of 5.5 months after treatment initiation. In addition to the seizure, one patient experienced severe pneumonia (grade III), and in one, gemcitabine administration had been delayed due to prolonged neutropenia. All other adverse events were mild (grade I-II). Salvage chemotherapy using erlotinib plus gemcitabine has very limited to no activity in patients with very advanced ACC.