Small cell lung cancer (SCLC) accounts for approximately 20% of all cases of lung cancer. It tends to disseminate early in the course of its natural history and to grow quickly. Approximately 10% to 18% of patients present with brain metastases (BM) at the time of initial diagnosis, and an additional 40% to 50% will develop BM some time during the course of their disease.
The aim of this review was to evaluate the effectiveness and toxicity of systemic chemotherapy for the treatment of BM from SCLC.
We searched the Cochrane Lung Cancer Review Group Specialised Register (July 2011), CENTRAL (2011, Issue 5), PubMed (1966 to July 2011), EMBASE (2005 to July 2011), LILACS (1982 to July 2011) and the International Clinical Trial Registry Platform (ICTRP).
Randomized controlled trials (RCTs) comparing systemic chemotherapy (single agent or combination chemotherapy) with another chemotherapy regimen, palliative care, whole brain radiotherapy or any combination of these interventions for the treatment of BM as the only site of progression.
Data collection and analysis
Data extraction and ‘Risk of bias’ assessment were carried out independently by two review authors. As the included studies evaluated three different treatment modalities meta-analysis was not possible.
Three RCTs, involving 192 participants, met inclusion criteria for this review. No significant differences for overall survival (OS) were reported in any of the trials: in the first trial, 33 patients received whole brain radiation therapy and no significant difference was found between patients treated with topotecan and those not treated with topotecan. In a second trial, in which 120 patients were randomized to receive teniposide with or without brain radiation therapy, the authors reported that the median progression-free survival (brain-specific progression-free survival (PFS)) was 3.5 months in the combined modality arm and 3.2 in the teniposide alone arm. In a third trial, comparing sequential and concomitant chemoradiotherapy (teniposide plus cisplatin) in 39 participants, the survival difference between the two groups was not statistically significant. While the first trial reported no significant difference in PFS, the second RCT found a significant difference favoring combined therapy group. The second trial also found that patients receiving chemoradiotherapy (teniposide plus whole brain radiotherapy) had a higher complete response rate than those receiving only the topoisomerase inhibitor.
Given the paucity of robust studies assessing the clinical effects of treatments, available evidence is insufficient to judge the effectiveness and safety of chemotherapy for the treatment of BM from SCLC. Published studies are insufficient to address the objectives of this review. According to the available evidence included in this review, chemotherapy does not improve specific brain PFS and OS in patients with SCLC. The combined treatment of teniposide and brain radiation therapy contributed to outcome in terms of increased complete remission and shorter time to progression (though not OS).
Plain language summary
Is chemotherapy beneficial to patients with brain metastases from small cell lung cancer?
Lung carcinoma is the single most common source of brain metastases (BM) in adults. Small cell lung cancer (SCLC) accounts for approximately 20% of all cases of lung cancer. It tends to disseminate early in the course of its natural history and to grow quickly. Approximately 10% to 18% of patients present with BM at the time of initial diagnosis, and an additional 40% to 50% will develop BM some time during the course of their disease.
After an extensive review of medical literature we identified three trials assessing different treatment strategies for patients with BM from SCLC. Only one of the studies compared chemotherapy (topotecan) versus no chemotherapy, but in patients treated with whole brain radiotherapy. Another study randomized patients to receive teniposide with or without brain radiation therapy, and the third one, compared sequential and concomitant chemoradiotherapy (teniposide plus cisplatin).
Studies show that people who received chemotherapy did not live longer or have a longer time before the BM grew again compared to those who were treated with brain radiation therapy alone. Hematological toxicities occurred more often in patients exposed to chemoradiotherapy in one study and in patients receiving sequential treatment in another study. A major limitation of this review was the low number of included studies and participants.