Small Cell Lung Cancer and Molecular Targeted Therapy
Small cell lung cancer (SCLC) is one of the major pathological types of lung cancer. Most of the patients with SCLC remain uncured with standard treatment consisting of platinum-based chemotherapy and have poor prognosis. The genomic characterization of S
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Small Cell Lung Cancer and Molecular Targeted Therapy Shunichiro Iwasawa Abstract Small cell lung cancer (SCLC) is one of the major pathological types of lung cancer. Most of the patients with SCLC remain uncured with standard treatment consisting of platinum-based chemotherapy and have poor prognosis. The genomic characterization of SCLC has not been fully elucidated, resulting that SCLC has significantly lagged behind NSCLC for the development of molecular targeted therapies. However, the development of sequencing technologies makes it possible to identify potent targets for the treatment in SCLC. A number of studies with various types of molecular targeted therapies have been conducted in patients with SCLC. Several molecular targeted agents showed promising efficacy with good tolerability but have not proven survival benefit in large clinical studies. Unfortunately, no molecular targeted agents have been approved for SCLC to date. Recently, immune checkpoint inhibitors have emerged as new promising therapeutic agents also in SCLC. These novel approaches are expected to improve clinical outcomes. In this chapter, currently available data of the molecular targeted therapies for SCLC and the future directions will be discussed. Keywords Small cell lung cancer (SCLC) • Chemotherapy • Molecular targeted therapy • Immune checkpoint inhibitor • Mutation
8.1 Introduction Small cell lung cancer (SCLC) is one of the major pathological types of lung cancer and accounts for approximately 15 % of all cases of the disease worldwide [1, 2]. The aggressive behavior of SCLC leads to high rate of late stage at diagnosis, recurrence, and mortality. The 5-year survival rate of SCLC is only 3.5–6.8 % [3, 4]. Since chemotherapy with cyclophosphamide showed a survival benefit over best S. Iwasawa (*) Department of Medical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, JAPAN e-mail: [email protected] © Springer Science+Business Media Singapore 2017 Y. Takiguchi (ed.), Molecular Targeted Therapy of Lung Cancer, DOI 10.1007/978-981-10-2002-5_8
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supportive care in the 1960s [5], chemotherapy has played an important role in the treatment of SCLC. For patients with limited disease (LD), concurrent chemoradiotherapy is the standard treatment which demonstrated a median survival time of −24 months [1, 6, 7]. In addition, prophylactic cranial irradiation (PCI) after complete response to chemoradiotherapy improved overall survival [8, 9]. For patients with extensive disease (ED), chemotherapy is the only standard modality of treatment. Platinum-based chemotherapy, including etoposide or irinotecan, showed a median survival time of 8–13 months [10, 11]. Although these treatment approaches have been established, most of the patients with SCLC remain uncured. A number of studies have been undertaken to overcome this situation. However, only slight progress has been made in the past decade. It seems that therapeutic ceiling has been reached in SCLC with chemotherapy.
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