title: Treatment of advanced adrenocortical carcinoma with erlotinib plus gemcitabine.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  The study consisted of case series collected from different centers (primary care and referral centers) in Germany in 2006-2007.
  
  
  METHODS
  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.
  
  
  METHODS
  We evaluated tumor response according to response evaluation criteria in solid tumors (RECIST) criteria after 12 wk of treatment.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Salvage chemotherapy using erlotinib plus gemcitabine has very limited to no activity in patients with very advanced ACC.
authors.affiliation: Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wortmann
authors.forename: Sarah
authors.initials: S
authors.lastname: Johanssen
authors.forename: Patrick
authors.initials: P
authors.lastname: Adam
authors.forename: Christian
authors.initials: C
authors.lastname: Ritter
authors.forename: Christian
authors.initials: C
authors.lastname: Ritte
authors.forename: Christian
authors.initials: C
authors.lastname: Strasburger
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D016879:Salvage Therapy; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine