Small cell lung cancer (SCLC) is highly sensitive to chemotherapy, but drug resistance appears early. Previous in vitro experiments have shown that for resistant SCLC cells, the chemotherapeutic drug concentration must be increased 3 to 5 times to achieve the same level of cytolysis as in sensitive cells. This is where the idea of high-dose chemotherapy comes from. Leyvraz et al. at the University Hospital of Lausanne, Switzerland, reported that for SCLC, increasing the chemotherapy dose to three times the standard dose not only did not help improve the prognosis but also produced more toxic effects, so the long-advocated dose augmentation strategy should be abandoned (J Natl Cancer Inst 2008, 100: 533). To investigate the effect of high-dose chemotherapy on the long-term survival of SCLC patients, this phase III randomized clinical trial randomized 140 patients with limited-stage or extensive-stage SCLC with ≤2 metastases into a high-dose chemotherapy group (69 patients) and a standard-dose chemotherapy group (71 patients) treated with different doses of ICE regimens (isocyclophosphamide + carboplatin + etoposide). The results showed that the relative dose intensity in the high-dose chemotherapy group was 293% of that in the standard-dose group; however, the 3-year survival rate, the primary study endpoint, was not significantly different between the two groups (18%; and 19%; in the high-dose and standard-dose groups, respectively), and the secondary study endpoints, total and complete effective rates, were also comparable between the two groups. -The total and complete effective rates were also comparable between the two groups (78%; vs. 68%; and 39%; vs. 34%; respectively). Subgroup (limited and extensive stage, with and without liver metastases, ECOG status scores 0 and 1, normal and abnormal lactate dehydrogenase levels) analysis found no regression benefit from high-dose chemotherapy. Consistent with the investigators’ prior estimates, severe myelosuppression occurred in the high-dose group, with grade 4 leukopenia and thrombocytopenia in all 61 patients who actually received chemotherapy, grade 3/4 anemia in 54, and 5 deaths from toxic reactions. In contrast, in the standard dose group, 49 patients developed ≥ grade 3 neutropenia, 17 each had anemia and thrombocytopenia, and 3 patients died from toxic reactions. In addition, nausea, vomiting, diarrhea, mucositis, and renal and neurological symptoms were more common and severe in the high-dose group.