BADULESCU F, CRISAN ANDA-ELENA, SCHENKER M.
Disciplina Oncologie, Facultatea de Medicină, U.M.F. din Craiova
REZUMAT
Rationamentul pentru care studiul markerilor moleculari in cancerele capului si gitului prezinta interes este imbunatatirea screeningului si diagnosticului (detectarea genelor hipermetilate in saliva pacientilor in faza preterapeutica care poate fi utilizat ca factor de predictie pentru decelarea recidivelor si ca screning populational), imbunatirea tratamentului (terapia moleculara tintita) si in monitorizarea postterapeutica (supravietuirea pacientilor cu mutatii p53 este statistic semnificativ mai mica, iar varianta p63 a genei p53 este corelata cu sensibilitatea la Cisplatin). Pacientii cu nivel seric crescut al EGFR (>50 ng/ml) au supravietuire statistic semnificativ mai buna, dar varianta vIII a EGFR (decelata in glioblastoame, cancer mamar, prostata, plamin si hiperexprimata in cancerele capului si gitului) este corelata cu descresterea supravietuirii si cu rezistenta la Cetuximab.
Chimioterapia de inductie urmata de radiochimioterapie este standardul terapeutic in cancerele capului si gitului avansate locoregional. Chimioterapia de inductie bazate pe regimuri cu 5FU/Platina determina o imbunatatire statistic semnificativa a supravietuirii la 5 ani cu 5% (p=0,05), iar radiochimioterapia concomitenta cu 8% (p<0.0001). Aditia Cetuximab la iradiere determina o imbunatatire semnificativa a controlului locoregional si a supravietuirii. Radiochimioterapia concomitenta cu Cetuximab ramine o alternativa eficienta pentru pacientii, care nu pot primii Cisplatin. Studiile viitoare urmaresc decelarea altor agenti terapeutici administrati concomitent cu radiochimioterapia concomitenta cu Cetuximab.
Chimioterapia de inductie cu administrare saptaminala Paclitaxel /Carboplatin +Cetuximab determina rate crescute de raspuns (RC: 81%), cu un control locoregional foarte bun. Insa rash-ul cutanat dupa Cetuximab a fost prezent la 50% din pacienti. Deasemenea aditia Cetuximab la Platina in linia I in cancerele capului si gitului recidivante/metastatice a determinat o imbunatatire statistic semnificativa a supravietuirii (HR:0.797, p=0.036). Supravietuirea mediana a fost imbunatatita cu 2,7 luni (de la 7,4 la 10,1 luni). Inhibitorii tirozinkinazici-Erlotinib/Gefitinib in asociere cu Docetaxel si Cisplatin este mai eficienta decit administrarea monochimioterapiei cu Erlotinib/Gefitinib, iar toxicitatea nu este mai mare decit in cazul administrarii Docetaxel/ Cisplatin singur. Tratamentele viitorului urmaresc asocierea agentilor antiVEGFR cu antiEGFR, respectiv antiEGFR cu inhibitori tirozinkinazici.
CUVINTE CHEIE Cancer cap si git, markeri moleculari, prognostic, tratament
Modern trends in the management of advanced locoregional head and neck cancer
ABSTRACT
The rationale for molecular detection in HNSC is improved screening and diagnosis (detected hypermethylated TSG promoters in pretreatment saliva from HNSC patients which can to be a surveillance model and prediction of recurrence and application to sceening population), improved treatment (target molecular terapie) and improved posttreatment monitoring (the surveillance of patients with mutant gene p53 is statistical smaller and the delta Np63 variant of p53 is correlated with Cisplatin sensitivity. The high level of serum EGFR (≥50 ng/ml) is associated with better survival, but the EGFR vIII (discovered in gliomas , carcinomas of breast, prostate ,lung and HNSCC ) is associated with decreases surveillance and resistant to Cetuximab. The consequenthy induction chemotherapy followed by chemoradiotherapy is standard therapy in head and neck cancer.
The induction chemotherapy (platinum/FU regimens) followed by local therapy determine a 5% absolut survival benefit at 5 years (p=0.05) vs local therapy alone ; also the concomitent chemoradiotherapy determine a 8% absolut survival benefit at 5 years (p<0.0001) vs radiotherapy alone. Addition of Cetuximab to radiotherapy improved locoregional control and survival. Radiotherapy plus Cetuximab will be an option for patients who can not receive CDDP.Studies ongoing to develop regimens incorporating Cetuximab with chemoradiotherapy .
Weekly Paclitaxel /Carboplatin plus Cetuximab as induction chemotherapy is highly active (primary site CR 81%) and the locoregional control was better. But sever skin rash affected nearly 50% of patients. Also the addition of Cetuximab to Platinum-based chemotherapy in the first-line treatment of recurrent/metastatic - SCCHN significantly prolonged overall survival (HR:0.797, p=0.036). Median overall survival was prolonged by 2,7 months with addition Cetuximab of chemotherapy arm compared to chemotherapy alone arm (7,4 to 10,1 months) Addition of Cetuximab did not modify the characteristic adverse event profile of platinum-based chemotherapy. Small molecular inhibitors –Erlotinib/Gefitinib plus Cisplatin and Docetaxel in recurrent/metastatic HNSCC demonstrated efficacy , especially Erlotinib vs Erlotinib/Gefitinib alone. The triplet combination did not cause more hematologic adverse events than would be expected using Docetaxel /Cisplatin