Chemotherapy in Small Cell Lung Cancer: The Current State of the Art

Although small cell lung cancer (SCLC) remains largely incurable, considerable progress has been made over the past 20 years in the development of combination chemotherapy regimens that significantly improve patient survival and quality of life. Several platinum plus etoposide regimens used alone, concomitantly with radiotherapy in limited-stage SCLC, or alternating with cyclophosphamide, doxorubicin, and vincristine are currently considered the treatments of choice for most patients. However, several other regimens of equal or nearly equal efficacy can be used, especially when patient occupation or other medical conditions, such as congestive heart failure, arrythmias, renal dysfunction, arthritis or pre-existing peripheral neuropathy, or hearing loss, require avoidance of cisplatin, doxorubicin, or vincristine. Although high-dose chemotherapy regimens aimed at exploiting an apparent dose-intensity-response relationship continue to be of interest, no data justify their routine use outside of a controlled clinical trial setting. Hematopoietic colony stimulating factors have been shown to reduce infectious complications, allow the maintenance of dose rates, and offer the potential that dose-intensive regimens might be investigated more safely. However, their high cost, the question of whether maintenance or intensification of dose rates is useful, and a report of an adverse radiation therapy interaction with granulocyte-macrophage colony-stimulating factor indicate that additional studies are needed to better define the role of this interesting class of agents in the treatment of this disease. Continued advances in autologous bone marrow transplantation technology that will allow safe administration of dose-intensive chemotherapy regimens, in the development of potent new microtubule and topoisomerse inhibitors (taxanes and camptothecins), and in identification of novel biological and molecular targets (autocrine growth factor loops and suppressor genes) hold great promise for significant improvements in the treatment of SCLC in the near future.