Chemotherapy (anticancer drugs) for patients with advanced small cell lung cancer

SmalI cell lung cancer accounts for nearly a quarter of all new cases of lung cancer. This cancer is often diagnosed in an advanced stage, which means that it has spread to the brain, liver, bone or bone marrow, and most patients die in the first year after diagnosis. This review found that first-line chemotherapy (anticancer drugs) may prolong the survival of patients with advanced small cell lung cancer for some months when compared to supportive care, although the effect of this treatment on quality of life is unknown. The benefit of a new treatment (second-line chemotherapy) when the disease has progressed or relapsed was even smaller, and the potential survival gain of some weeks must be balanced against its possible secondary effects. Since the available studies were scarce and of variable quality, more clinical trials are needed to assess and better inform patients about the real effectiveness of chemotherapy in advanced small cell lung cancer.

Authors' conclusions: 

Two small RCTs from the 1970s suggest that first-line chemotherapeutic treatment (based on ifosfamide) may provide a small survival benefit (less than three months) in comparison with supportive care or placebo infusion in patients with advanced SCLC. However platinum-based combination chemotherapy regimens have been shown to increase complete response rates when compared to non-platinum chemotherapy regimens with no significant difference in survival, and so these are currently the standard first-line treatment for patients with SCLC.

Second-line chemotherapy at relapse or progression may prolong survival for some weeks in relation to BSC. Nevertheless, the impact of first-line chemotherapy on quality of life, older patients, women and patients with poor prognosis is unknown and the benefits of second-line chemotherapy are also unclear for older people. Globally, the evidence on which these conclusions are based is very scarce and of uncertain or low quality, which calls for well-designed, controlled trials to further evaluate the trade-offs between benefits and risks of different chemotherapeutic schedules in patients with advanced SCLC.

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Background: 

Combination chemotherapy has been the mainstay of treatment for extensive stage small celI lung cancer (SCLC) over the last 30 years, even though it only gives a short prolongation in median survival time. The main goal for these patients should be palliation with the aim of improving their quality of life.

Objectives: 

To determine the effectiveness of first-line chemotherapy versus placebo or best supportive care (BSC) in prolonging survival in patients with extensive SCLC at diagnosis and the effectiveness of second-line chemotherapy at relapse or progression after first-line chemotherapy compared with BSC or placebo in prolonging survival in patients with extensive SCLC; as well as to evaluate the adverse events of treatment and the quality of life of patients.

Search strategy: 

This is the second update of the review. MEDLINE (1966 to October 2013), EMBASE (1974 to October 2013), and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 3) were searched. Experts in the field were contacted.

Selection criteria: 

Phase III randomised controlled trials in which any chemotherapy treatment was compared with  placebo or BSC in patients with extensive SCLC, as first-line or second-line therapy at relapse.

Data collection and analysis: 

Two authors independently extracted data and assessed study quality. We resolved disagreements by discussion. Additional information was obtained from one study author.

Main results: 

Two studies of unclear risk of bias were included for first-line chemotherapy. A total of 88 men under 70 years with good performance status were randomised to receive either supportive care, placebo infusion or ifosfamide. Ifosfamide gave an extra mean survival of 78.5 days compared with supportive care or placebo infusion. Partial tumour response was greater with the active treatment. Toxicity was only seen in the chemotherapy group and quality of life was only assessed at the beginning of treatment. The quality of the evidence for overall survival and adverse effects was very low.

Three studies of moderate risk of bias were included for second-line chemotherapy at relapse (one identified in the last search). A total of 932 men and women under 75 years and any performance status were randomised to receive either methotrexate-doxorubicin, topotecan, or picoplatin versus symptomatic treatment or BSC. The methotrexate-doxorubicin treatment gave a median survival of 63 days longer than in the symptomatic-treatment group for patients allocated to receive four cycles of first-line chemotherapy, and 21 days longer for patients allocated to receive eight cycles of first-line chemotherapy.

Treatment with topotecan gave a median survival of 84 days longer than in the BSC group (log-rank P = 0.01). The adjusted hazard ratio (HR) for overall survival was 0.61 (95% CI 0.43 to 0.87). Treatment with picoplatin gave a median survival time of six days longer than BSC (HR 0.817, 95% CI 0.65 to 1.03, P = 0.0895). A meta-analysis of topotecan and picoplatin gave a HR of 0.73 (95% CI 0.55 to 0.96, P = 0.03; low-quality evidence).

Partial or complete response in the methotrexate-doxorubicin group was 22.3%. Five patients (7%, 95% CI 2.33 to 15.67) showed a partial response with topotecan. No data were provided about tumour response in the picoplatin study. Toxicity was worst in the chemotherapy group (moderate-quality evidence). Quality of life was better in the topotecan group and was not measured in the methotrexate-doxorubicin and picoplatin studies (low-quality evidence).

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