Recent Trend in The Treatment of Non-Small Cell Lung Cancer Non-small cell lung cancer

Lee, Kye Young

Abstract

(NSCLC) accounts for more than 80% of all lung cancer cases. Even though surgery plays a key role in the curative management of NSCLC, especially the stage I or II disease, 80%, or more, of NSCLC patients have the locally advanced or disseminated disease. Despite the tremendous progress made in the molecular biological understanding of lung cancer during recent decades, the overall 5-year survival rate still remains very disappointing. The stage of the disease at diagnosis is the most important factor in the choice of treatment. For patients with the stage I or II disease, surgery is central to most management plans. Except for the stage IA disease, roughly 50% of surgical patients eventually relapse; more frequently in the metastatic form rather than from a local relapse. Randomized trials have not found consistent survival benefits with the use of postoperative (adjuvant) chemotherapy or radiation. However, the role of induction chemotherapy in the early stages of NSCLC is under investigation. The management of the stage III locally advanced disease is complicated, and although the stage IIIA disease has been considered borderline for an operation, there is still substantial controversy in the management of the N2 disease. Minimal N2 is a definite surgical indication, but the clinically evident N2 disease is generally regarded as unresectable. The standard management of the resectable IIIA disease is moving toward neoadjuvant treatment, followed by surgery. Approximately 40% of NSCLC patients present with a locally advanced, unresectable disease. Traditionally radiotherapy has been the treatment of choice in these patients, but their long-term survival is very poor. The recent development of new radiation techniques to enhance local control, including altered radiation fractionation schedule or three-dimensional treatment planning techniques, might further improve survival outcomes. Nevertheless, multimodality therapy, with a combination of chemotherapy and radiation, has recently become the mainstream in the management of these diseases. The newer chemotherapeutic agents, such as paclitaxel, docetaxel and gemcitabine, have been proven to have a radio sensitizing effect. A comparison of the efficacy and toxicity of concurrent vs. sequential chemoradiotherapy is currently underway to compare. The stage IV and IIIB diseases, with malignant effusion, are candidates for systemic chemotherapy. In the last decade, cisplatin-based regimens have been shown to prolong survival, improve symptom control and the quality of life. The introduction of gemcitabine, vinorelbine, paclitaxel, docetaxel and irrinotecan has raised the possibility of new platinum-based combination drugs. However, there is no clear superiority of the various new combination regimens, which could lead to the possibility of customize chemotherapy on an individual basis, according to the toxicity profiles. Most recently targeted therapy has opened new horizons. The introduction of biological agents, which target highly specific intracellular pathways, could potentially enhance the efficacy of cytotoxic chemotherapy. The anti-EGFR agents ZD 1839 (Iressa) and cetuximab (C225, Erbitux) have been clinically investigated, and preclinical evidence of an additive or synergistic interaction, with chemotherapy, is also available for farnesyl transferase inhibitors, matrix metalloproteinase inhibitors, adenovirally-mediated p53 gene transfer, selectively replicating adenovirus ONYX-015 and flavopiridol.