Small cell lung cancer: Strategies to optimize chemotherapy response

During the past two decades, a major focus of clinical research in small ce ll lung cancer (SCLC) has been the manipulation of the dose and schedule of the available active cytotoxic agents. Approaches tested include alternati ng cyclic combination chemotherapy, increasing the dose intensity of chemot herapy with or without the support of either cytokines or stem cells, and i ncreasing the dose density by delivering treatment at shorter intervals. Ov erall, the results of clinical trials testing these approaches have been di sappointing. One of the difficulties in intensifying treatment for SCLC is that the patients tend to be elderly and have smoking-related pulmonary and cardiovascular comorbidities. In fact, as treatment regimens have become m ore intensive, several multicenter groups have identified a dramatic increa se in early-treatment-related mortality rates. Yet, toxicity associated wit h dose-intensification may obscure a potential therapeutic advantage in uns elected patients. Therefore, some of these groups have performed retrospect ive analyses to identify factors that predict excessive treatment-related t oxicity that can be used for patient stratification in clinical trials. Thi s article reviews the data regarding the role of dose-intensified therapy i n the treatment of SCLC. We propose that delivery of the currently availabl e chemotherapy drugs at greater dose intensity, if excessive toxicity is av oided, may offer a meaningful improvement in survival, and that clinical tr ials that appropriately test this hypothesis are warranted.