Context: 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 are the recommended first-line therapies. However, many patients have progressive disease despite treatment with these regimens.

Objective: To evaluate the efficacy of the EGFR inhibitor erlotinib plus gemcitabine as salvage therapy in ACC patients with very advanced ACC.

Design/Setting: Case series collected from different centers (primary care and referral centers) in Germany in 2006–2007

Patients and Intervention: Patients registered with the German ACC registry with progressive ACC after 2–4 prior systemic therapies were offered treatment with erlotinib and gemcitabine. Oral erlotinib (100 mg/d) was administered on a daily basis and gemcitabine (800 mg/m2) intravenously every 14 days.

Main Outcome Measure: Evaluation of tumor response according RECIST criteria after 12 weeks of treatment.

Results: Ten patients have been treated with erlotinib and gemcitabine. Only 1/10 patients experienced a minor response (progression-free survival 8 months), whereas 8 patients had progressive disease at the first staging. One patient had to stop therapy after the first administration of gemcitabine due to cerebral seizure. 9/10 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 administrations had been delayed due to prolonged neutropenia. All other adverse events were mild (grade I-II).

Conclusions: Salvage chemotherapy using erlotinib plus gemcitabine has very limited to no activity in patients with very advanced ACC.