CHEMOTHERAPY OF LUNG CANCER: STATE-OF-THE-ART

Chemotherapy plays a major role in the treatment of patients with lung cancer. The type of chemotherapy of lung cancer depends on tumor histology, disease stage, molecular tumor features, and patient characteristics. First-line chemotherapy of small-cell lung cancer consists of a platin (cisplatin or carboplatin) plus etoposide. At the time of progressive disease, patients receive second- line chemotherapy with topotecan or other regimens. Chemotherapy of non-small-cell lung cancer (NSCLC) is also well established. Patients with advanced NSCLC receive palliative chemotherapy which decreases cancer- related symptoms and prolongs survival of patients. First-line chemotherapy consists of a platin combined with a 3rd generation anticancer drug. Selection of the chemotherapy regimen is based on risk factors as well as co-morbidity of patients, toxicity profile, convenience of administration, and costs. Patients receive 4 to 6 cycles. In patients with predominantly non-squamous cell NSCLC, chemotherapy is combined with bevacizumab. Patients with poor performance status and elderly patients also benefit from palliative chemotherapy with well tolerated regimens. Elderly patients with good performance status and adequate organ function may also be considered for a platin-based doublet. Maintenance therapy with pemetrexed or erlotinib is a treatment option for selected patients. Second-line therapy at the time of progressive disease consists of docetaxel, pemetrexed or erlotinib. Recently, targeted therapies have been established for patients with EGFR mutations or ALK translocations in their tumors. In patients with EGFR mutation-positive tumors, tyrosine kinase inhibitors (gefitinib,erlotinib, afatinib) have resulted in longer progression-free survival and better quality of life compared to first-line chemotherapy and, therefore, have become the preferred first-line therapy for these patients. In patients with ALK-positive tumors and previously treated with chemotherapy, crizotinib prolonged progression-free survival compared to chemotherapy (docetaxel or pemetrexed) and, therefore, has been approved as second-line therapy for these patients. Chemotherapy is also an important part of the multimodality therapy in patients with locally advanced NSCLC. Chemotherapy should preferentially be based on a cisplatin- based doublet. Chemotherapy administered concurrently with radiotherapy has been shown to be superior to sequential administration of both treatments. Adjuvant chemotherapy with cisplatin-based regimens increases the 5-year survival rate by 5% and has been established for patients with completely resected stages II and III of NSCLC. Patients receive four cycles of a platin- based doublet, preferentially cisplatin plus vinorelbine. Further improvements in clinical outcome are anticipated through the addition of bevacizumab, erlotinib or tumor vaccines.