main tumour sites are the sacrum ( 5060% ) , the skull base ( 2535% ) and the spine , mainly cervical ( 15% ) . lung , bone , liver or soft tissue metastases sometimes arise , but local recurrence is the main cause of death [ 1 , 2 ] . initial treatment is based on complete surgical resection . however , safe margins are difficult to achieve due to the vicinity of vital or functional anatomic structures . radiation therapy is often performed after surgery to limit the risk of a local recurrence . proton beam therapy is the most recommended technique in order to deliver a high dose to the tumour with limited damage to adjacent tissues . conventional cytotoxic drugs are not active against this tumour type . a modest but significant activity of imatinib , an inhibitor of platelet - derived growth factor receptor ( pdgfr ) and c - kit , has been described in several case reports and in a phase ii study [ 4 , 5 , 6 ] . more recently , clinical activity of erlotinib , a tyrosine kinase inhibitor of the epidermal growth factor receptor ( egfr ) , was observed [ 7 , 8 , 9 , 10 ] . we report a new , well - documented case of a locally advanced chordoma that responded to erlotinib after the failure of imatinib . an mri showed a heterogeneous mass involving the sphenoid bone , with suprasellar and left cavernous sinus extension . histological analysis demonstrated the presence of large cells disposed in heaps with round nuclei leading to the diagnosis of clivus chordoma . a second partial surgical resection was performed in january 2006 due to tumour progression into the upward sella and close contact to the chiasma . diplopia recurred in october 2009 due to paralysis of the right abducens nerve ( vi ) . in september 2011 , ptosis of the right palpebra developed , and it was accompanied by a deficit of the right oculomotor nerve ( iii ) and by mydriasis . imatinib ( 400 mg / day , then 800 mg / day ) was given for 5 months , but the tumour nevertheless progressed toward the frontal lobe ( fig . to date ( july 2014 ) , ptosis persists , but without any new neurological symptoms . the tolerance of erlotinib was relatively good , with a moderate rash on the face and diarrhea that was controlled by loperamide . activation of pdgfra and pdgfrb was documented in chordoma [ 11 , 12 ] , leading to the clinical evaluation of imatinib , a pdgf inhibitor [ 4 , 5 ] . a phase ii study has been completed using 800 mg / day imatinib . among 50 patients , egfr expression and activation is also involved in chordoma progression . in the first study investigating egfr expression in chordoma , another study reported an egfr expression in 83% of primary chordomas and 97% of recurrent chordomas among 52 patients , while a third study showed that the egfr was expressed in 60% of chordomas and activated in 50% of cases among 173 chordomas . egfr is then the most significantly activated receptor tyrosine kinase in chordomas , and therefore a potential therapeutic target . in vitro studies have shown that pharmacological inhibition of egfr had an anti - tumour effect on the u - ch1 human chordoma cell line . tyrphosin ( ag1478 ) , an egfr inhibitor , diminished cell proliferation and egfr phosphorylation . erlotinib limits egfr phosphorylation by binding to the intracellular part of the egfr tyrosine kinase domain . downstream inhibition of the ras / mek pathway inhibits the proliferation and survival of sensitive cancer cells . activation of egfr by egf enhanced cell proliferation in vitro , but erlotinib decreased proliferation of the u - ch1 and c24 human chordoma cell lines in a dose - dependent fashion [ 16 , 17 ] . in the same study , treatment of a patient - derived xenograft with erlotinib resulted in a significant reduction of tumour volume compared to control , and molecular analyses revealed reduced phosphorylation of the tyr845 residue of egfr . this molecular rationale led to a compassionate use of erlotinib in patients with relapsed chordoma , especially when the disease progressed despite imatinib treatment . to date , there are 4 case reports describing the activity of erlotinib when used in association with bevacizumab in chordoma [ 9 , 10 ] . the role that can be ascribed to erlotinib is then difficult to define , but to our knowledge , bevacizumab alone has no effect on chordoma . only 2 case reports have described a tumour response with erlotinib treatment alone . in the first case , a 30% tumour reduction was observed with erlotinib treatment in a sacral metastatic chordoma with gluteal mass and iliac lymph nodes that was resistant to imatinib . a 70% regression of a thoracic chordoma with lung metastases and cervical lymph nodes were registered after 7 months of erlotinib treatment , while the disease was refractory to imatinib . our study is the 7th study to be published to date investigating the role of erlotinib in chordoma , and the third using erlotinib alone . here , we report the longest response duration to erlotinib described in the literature to date ( 28 + months ) . our case report corroborates previous studies , showing that erlotinib is an effective drug in patients with advanced chordoma , even those refractory to imatinib . a prospective clinical trial comparing erlotinib and imatinib as a first - line treatment of recurrent chordoma is mandatory .
chordoma is a rare malignant axial tumour that develops from embryonic remnants of the notochord . 
 surgery and irradiation are the standard initial treatment . 
 however , local recurrence is frequent and cytotoxic chemotherapy is inefficient . 
 transient activity of imatinib , a platelet - derived growth factor receptor inhibitor , was described in a phase ii study . 
 activity of epidermal growth factor receptor ( egfr ) inhibitors ( erlotinib , gefitinib ) has also been shown in a few recent case reports . 
 we describe a 68-year - old female in whom clivus chordoma recurred after surgery and radiotherapy . 
 the tumour progressed despite imatinib treatment . a partial and sustained response 
 ( 28 + months ) was obtained using erlotinib , an egfr inhibitor . 
 erlotinib should be evaluated in a prospective trial investigating new potential therapies against recurrent chordoma .