Treatment of advanced adrenocortical carcinoma with erlotinib plus gemcitabine.
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.
Quinkler
Marcus
M
Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Germany.
Hahner
Stefanie
S
Wortmann
Sebastian
S
Johanssen
Sarah
S
Adam
Patrick
P
Ritter
Christian
C
Ritte
Christian
C
Strasburger
Christian
C
Allolio
Bruno
B
Fassnacht
Martin
M
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
D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine