Experimental approaches to treatment for small cell lung cancer
- Karen Kelly, MD
Karen Kelly, MD
- Professor of Medicine
- University of California Davis Cancer Center
- Section Editors
- Rogerio C Lilenbaum, MD, FACP
Rogerio C Lilenbaum, MD, FACP
- Section Editor — Lung Cancer
- Yale Cancer Center
- James R Jett, MD
James R Jett, MD
- Section Editor — Lung Cancer
- Professor of Medicine Emeritus
- National Jewish Health
Small cell lung cancer (SCLC) is distinguished from non-small cell lung cancer (NSCLC) by its rapid doubling time, high growth fraction, and the early development of metastases. Although SCLC is highly responsive to both chemotherapy and radiotherapy (RT), it commonly relapses within months despite treatment.
Since SCLC usually presents with disseminated disease, treatment strategies have focused on systemic chemotherapy. Although this has resulted in significant improvements in survival for patients with both limited and extensive stage disease, the long-term prognosis remains poor.
Attempts to further improve survival with chemotherapy have included the evaluation of higher dose therapy including bone marrow transplantation, dose dense regimens, alternating non-cross resistant treatments and novel cytotoxic agents. However, these approaches have not resulted in major advances in the treatment of SCLC in more than twenty years. (See "Extensive stage small cell lung cancer: Initial management", section on 'Increased dose intensity'.)
Investigational approaches for the treatment of SCLC will be reviewed here. Standard approaches to chemotherapy in patients with SCLC are discussed separately. (See "Extensive stage small cell lung cancer: Initial management" and "Treatment of refractory and relapsed small cell lung cancer".)
Angiogenesis is necessary for tumor growth and metastasis. Pathologic studies in resected small cell lung cancer (SCLC) specimens revealed that high microvessel count and vascular endothelial growth factor (VEGF) expression were associated with decreased survival [1,2]. Furthermore, VEGF expression was shown to be an independent poor prognostic factor, as was a high pretreatment level of VEGF [1,2].
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- ANGIOGENESIS INHIBITORS
- Oral angiogenesis inhibitors
- Other VEGF inhibitors
- MOLECULARLY TARGETED THERAPIES
- Aurora A kinase inhibitor
- PARP inhibitors
- PI3K/Akt/mTOR inhibitors
- Other agents
- - IGF-1R inhibitors
- - Hedgehog inhibitors
- - Tyrosine kinase inhibitors
- - Apoptosis modulators
- Other classes of molecular therapies
- Checkpoint inhibition
- - Anti-PD1 antibodies
- - Ipilimumab
- Tumor vaccines
- Other immunotherapy approaches
- CYTOTOXIC CHEMOTHERAPY