Treatment of refractory and relapsed 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) represents 15 percent of all lung cancers and occurs almost exclusively in smokers. It is distinguished from non-small cell lung cancer by its rapid doubling time, high growth fraction, and the early development of widespread metastases. Although considered highly responsive to chemotherapy and radiotherapy, SCLC usually recurs within 14 to 15 months for patients with limited-stage SCLC and five to six months for patients with extensive-stage SCLC. Many of these patients are candidates for additional systemic treatment.
The median survival of patients with relapsed SCLC ranges from two to six months. The most important factors affecting prognosis are performance status, tumor extent (ie, limited versus extensive), and time to relapse after first-line therapy . Similarly, the likelihood of an objective response to second-line therapy depends upon the time from last therapy to relapse, the response to initial treatment, and the performance status.
The treatment of relapsed and refractory SCLC will be reviewed here. The initial management of SCLC and experimental approaches to treatment are considered separately. (See "Extensive stage small cell lung cancer: Initial management" and "Limited stage small cell lung cancer: Initial management" and "Experimental approaches to treatment for small cell lung cancer".)
GOALS AND EFFICACY OF CHEMOTHERAPY
Second-line chemotherapy generally is less effective than the initial treatment, but it can provide significant palliation for many patients. Symptom control and improved quality of life are the primary goals of treatment, and these must be clear to both patients and their families. While chemotherapy has been associated with improved quality of life outcomes , prolonged survival, increased time to tumor progression, and a reduction in tumor burden may also be achieved in some patients.
Single-agent chemotherapy generally is preferred because combination chemotherapy is associated with greater toxicity without an efficacy benefit . An exception to this approach is the use of the initial platinum-based combination chemotherapy for patients with a late relapse (>6 months). (See 'Sensitive disease (relapse after 90 days)' below.)
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- GOALS AND EFFICACY OF CHEMOTHERAPY
- REGIMEN SELECTION BY LENGTH OF RELAPSE-FREE SURVIVAL
- Refractory disease (no response)
- Resistant disease (relapse within 90 days)
- Sensitive disease (relapse after 90 days)
- Efficacy of therapies
- - Topotecan and irinotecan
- - Other agents
- Treatment duration and further lines of therapy
- SPECIAL CONSIDERATIONS
- Late relapses (after six months)
- Poor performance status
- Brain metastases
- INVESTIGATIONAL APPROACHES
- - Checkpoint inhibition
- Anti-PD-1 antibodies
- Other experimental options
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS