Topotecan for the treatment of relapsed small-cell lung cancer

Lung cancer can be categorised into 4 major cell types: small-cell lung cancer, squamous-cell carcinoma, adenocarcinoma and large-cell carcinoma. The last 3 types are usually described as non-small-cell lung cancer. Small-cell lung cancer grows rapidly and spreads quickly to distant sites (metastasises). It is classified using a 2‑stage system. The first is limited-stage disease, in which the disease is generally confined to 1 side of the chest or to the neck lymph nodes. The second is extensive-stage disease, in which the disease has spread outside 1 side of the chest and there are systemic metastases. The 'tumour node metastases' stage scores are not usually relevant in small-cell lung cancer because of the high proportion of patients presenting with metastases and the poor prognosis associated with the disease.

Lung cancer is 1 of the most common cancers in England and accounted for 15% of cancers in men and 11% of cancers in women in 2005. In England and Wales there were 33,181 new cases of lung cancer in 2005. The disease accounts for around 33,000 deaths per year. It is estimated that small-cell lung cancer makes up about 10% to 20% of the total cases of lung cancer, but this percentage is falling. The reasons for this are unclear, but changing smoking habits and a reduction in the tar content of cigarettes may be involved. At diagnosis, about 33% of people with small-cell lung cancer have limited-stage disease, but the majority of people have extensive-stage disease.

In most patients the disease is symptomatic on presentation. In some patients there are non-specific symptoms such as fatigue, loss of appetite and weight loss, while in others there are more direct symptoms such as breathlessness, chest discomfort and haemoptysis (blood-stained sputum). The risk factors for lung cancer include smoking, passive smoking, occupational exposure to asbestos, radon, chromium or nickel, male gender and chronic lung disease. Smoking is the leading cause of lung cancer, accounting for approximately 80% to 90% of cases. Smoking has been shown to be much more strongly linked to small-cell lung cancer than non-small-cell lung cancer.

The prognosis for people with small-cell lung cancer is poor. Without treatment, it has an aggressive clinical course with a life expectancy of approximately 3.5 months for limited-stage disease and 6 weeks for extensive-stage disease. The median survival with treatment is approximately 14 to 18 months for limited-stage disease and 9 to 12 months for extensive-stage disease. Approximately 20% to 40% of patients with limited-stage disease and less than 5% of patients with extensive-stage disease survive for 2 years. Survivors often continue to relapse up to, and occasionally after, 5 years. Prognosis has been linked to performance status and the extent of the disease.

Selection of the most appropriate first-line treatment for small-cell lung cancer is determined primarily by the performance status of the patient and the stage of the disease. Current management of small-cell lung cancer usually consists of combination chemotherapy regimens. Radiotherapy may be given concurrently with chemotherapy or as part of palliative care. Surgery is not appropriate for the majority of patients because the disease is often widespread at the time of diagnosis. For further guidance on the management of small-cell lung cancer, see NICE's guideline on lung cancer.