Systemic Therapy for Lung Cancer for the Radiation Oncologist

摘要: Worldwide, approximately 1.6 million new cases of lung cancer are diagnosed each year. It continues to be the leading cause death. With use systemic therapy in addition radiation and surgical resection, outcome all patients improve. There is an absolute improvement not only overall survival (OS) but also quality life these patients, though modest at best. Non-small cell (NSCLC) accounts for 87% cancers, subdivided into two major types, nonsquamous carcinoma squamous carcinoma, former including adenocarcinoma, large bronchioloalveolar poorly differentiated histological subtypes. Most present after NSCLC have spread regional or distant sites. Patients presenting with advanced, unresectable disease (stage IIIB IV) who develop recurrent metastatic following resection candidates therapy. Even early stage resected improved OS adjuvant urgent need novel effective regimens as current therapies do offer a curative potential palliative benefits restricted good performance status (Eastern Cooperative Oncology Group 0 1). The cisplatin-pemetrexed regimen has demonstrated preferential activity non-squamous histology. Pemetrexed erlotinib recently emerged option maintenance advanced four cycles combination chemotherapy change treatment paradigm. Epigenetic alterations been linked pathogenesis progression they lead inhibition transcription key cycle regulatory genes. Vorinostat (SAHA), functional effects on histone acetylation attempts restore normal Provocative noted vorinostat NSCLC. Thus, HDAC inhibitors class agents that will require extensive evaluation cancer. Bevacizumab, monoclonal antibody against vascular endothelial growth factor (VEGF), was first agent demonstrate (ECOG 4599) increase toxicity bevacizumab calls caution selecting VEGF tyrosine kinase (TKIs) appear promising, unique toxicities such hand–foot syndrome fatigue hypertension. remains seen whether TKI surpass efficacy bevacizumab-chemotherapy regimens. Identification predictive biomarkers patient selection elusive anti-angiogenic agents. Molecular markers increasingly being utilized personalize presence activating mutation epidermal receptor (EGFR) associated high response rates PFS EGFR TKIs. This already led first-line sensitive mutation. For wild-type (or if unknown) ‘standard care’ second generation currently under evaluation. studies evaluate definitive role ALK inhibitor translocation EML 4- gene progress. Other interest include: Excision repair cross-complementing 1 (ERCC1), RRM1, thymidylate synthase (TS), K-ras mutation, c-met expression/mutation, TRAIL R2, IGF-1R, JAK-2 list goes on. Thus focus research proper optimizing effect molecularly targeted identification validation biomarkers.