Modern management of small-cell lung cancer

In this article, we review best standard practice for the management of small-cell lung cancer (SCLC) and indicate the likely areas of development over the next 5-10 years. A number of prognostic scores have been developed and these allow more rational decisions on treatment. Treatment with cisplatin plus etoposide with early, concurrent radiotherapy is the standard of care for patients with limited-stage disease (LD) suitable for this approach. A 5-year survival rate of 25% has been reported for concurrent hyperfractionated radiotherapy; however, the applicability of this in most busy hospitals is uncertain and this treatment is currently being compared with a high-dose, once-daily regimen. Patients unsuitable for concurrent chemo-radiotherapy are treated with a sequential approach. Patients with LD responding to treatment should be offered prophylactic cranial irradiation (PCI). A variety of strategies for improving survival have been investigated. Intensification of chemotherapy has not shown any clear survival advantage, but maintenance of dose intensity in patients with good prognosis is important. The evidence around maintenance therapy is conflicting and this is not routinely used. Patients with extensive-stage disease but few other adverse prognostic factors should be treated with a platinum compound plus etoposide, and carboplatin is a reasonable choice. Responding patients should be offered PCI as this is associated with a survival benefit. The initial positive results for irinotecan have not been repeated in a larger study. Age is not a prognostic factor, but caution needs to be exercised as prognostic scores do not reflect co-morbidity. Patients with relapsed disease have a poor prognosis, but there is evidence of a survival benefit for salvage chemotherapy in those fit for treatment. The choice of treatment will depend on a number of factors, including the disease-free interval. Topotecan is the only drug licensed in this indication, but myelosuppression is considerable. A number of new drugs are under evaluation and showing promise in SCLC. One of the most promising of these is amrubicin. A large randomised study has failed to show any benefit from the addition of thalidomide to chemotherapy with carboplatin and etoposide in extensive-stage disease patients responding to chemotherapy. Studies of a number of targeted treatments are also ongoing. The challenge for the future is to identify new targets, overcome drug-resistance mechanisms and redundancy in biological systems, and incorporate these new treatments into concurrent chemo-radiotherapy schedules.