Importance of dose and dose intensity in the treatment of small-cell lung cancer

 This review examines the rationale and outcomes of intensive chemotherapy trials for small-cell lung cancer (SCLC) to determine whether further clinical research in this area is likely to generate improved results. Animal model experiments for intensive chemotherapy were reviewed to determine whether results observed in the laboratory predicted the outcomes seen in clinical trials. In addition, phase III randomized trials that differ only by the quantity of chemotherapy drug delivered were examined, with particular attention being paid to whether the conclusions reached were consistent when limited-stage and extensive-stage SCLC were separately studied. The most clear-cut evidence of benefit in animal model experiments comes from models with curative potential. In clinical trials, when dose and dose intensity are diminished from standard levels the effect is detrimental for both limited- and extensive-stage SCLC. Trials of dose and dose intensity above standard levels have not yet shown advantages for patients with extensive-stage SCLC. However, the only two randomized trials of chemotherapy dose escalation for limited-stage SCLC show statistically significant survival benefits. Therefore, animal model experiments have accurately predicted conclusions reached in SCLC clinical trials. Future studies of intensive chemotherapy for SCLC should focus on the limited-stage group.