Chemotherapy in small cell lung cancer.

Chemotherapy is the backbone in the treatment of small cell lung cancer (SCLC) and radiotherapy is an important adjunct in limited stage disease. The role of chest irradiation is now documented in three meta-analysis, based on the same body of data. Trials on timing, scheduling and fractionation could have followed a more stringent development line but altogether, the highest efficacy seems to be obtained with early, concurrent twice-daily chest irradiation. Patients in complete remission should have prophylactic cranial irradiation, which reduces the risk of brain metastases and of death from SCLC. Four series of chemotherapy seem to be sufficient in limited-stage disease while six is recommended in extensive disease. The combination of etoposide plus cis- or carboplatin is appropriate in both stages and addition of other agents has no clinically important impact on the survival. Use of haematological growth factors such as granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) may enable higher doses or more frequent dosage. Three randomized trials on GM-CSF showed a negative outcome while G-CSF support may result in better survival rates, but a more cost-efficient policy must be found. High-dose chemotherapy plus haematological stem-cell support is still under investigation but disappointing long-term survival rates means there is not much optimism for this strategy. New strategies in general are requested in the treatment of extensive-stage disease and of elderly patients. Phase II trials suggest that good-risk patients with extensive disease should be treated aggressively, intermediate-risk patients more gently, and palliation must be the primary aim in the treatment of poor-risk patients. In elderly patients impressive survival rates are obtained with 3-4 series of chemotherapy and radiation delivered in 5-10 fractions. A number of new agents are active but more trials are required before each has found a place, if any, in the treatment of small cell lung cancer. To conclude, the randomized trial is still an important instrument in clinical oncology, and trials in small cell lung cancer must be large, which is why the cooperation of organizations and multicentres is urgent.