Novel Therapeutic Approaches for Small Cell Lung Cancer: The Future has Arrived

Abstract

Thirty thousand patients are diagnosed with small cell lung cancer (SCLC) in the United States each year [1]. Tobacco exposure is strongly associated with the development of this disease. SCLC has a unique natural history with a much shorter doubling time, higher growth fraction and earlier development of widespread metastases than any of the non-small cell histologies. Although SCLC is characterized by a superior initial response rate to chemotherapy and radiation, even responsive disease is typically associated with relapse within months after treatment, with the rapid development of chemo-resistance, leading to a dismal five year survival rate of 5% [2]. Few improvements have been made in the fundamentals of SCLC treatment. Notably, the standard chemotherapy regimen used for initial disease has not changed over the last three decades. First-line treatment for SCLC involves combination chemotherapy with cisplatin or carboplatin plus etoposide (with the addition of radiation therapy in limited stage), which results in a 60-80% overall response rate. However, all patients with extensive stage SCLC, and the majority of patients with limited SCLC, suffer relapse within months of completing initial therapy. Topotecan (Hycamtin; GlaxoSmithKline) is the only approved agent for recurrent or progressive SCLC, based on the results of three phase III trials [3-5]. There are no accepted regimens for patients whose disease has progressed after first- and second-line treatments for SCLC. As the prognosis for patients with recurrent SCLC is poor, there is a clear need for the development of new therapeutic strategies. Focusing on common tumor-specific molecular and cellular abnormalities may identify novel therapeutic targets in this challenging disease.