OBJECTIVES: .  Meaningful improvement in symptoms and quality of life (QOL) are important in treating patients with small cell lung cancer (SCLC).  This analysis assessed and evaluated minimally important differences (MIDs) on the Lung Cancer Symptom Scale (LCSS) for patients with amrubicin- or topotecan-treated SCLC. METHODS: .  A prospective, multicenter, open-label, phase III randomized design study of 637 patients compared efficacy and safety of amrubicin to topotecan in treatment of SCLC.  LCSS data were collected at baseline, day 1 of each cycle, and study end.  The LCSS contains six symptoms (appetite, cough, dyspnea, fatigue, hemoptysis, pain), and three items (symptom distress, interference with activity level, global QOL).  To assess clinically meaningful change on LCSS symptoms, MIDs were calculated as ½ standard deviation change from baseline for each symptom item; for Symptom Burden Index (SBI) and Total Score, 1 standard error of measurement change from baseline was utilized to adjust for reliability in the SCLC population. RESULTS: .  532 subjects with baseline and post-baseline LCSS data were analyzed (mean age=60.1; male 58.2%).  Clinically relevant minimally important symptom and QOL worsening were similar to studies in non-small cell lung cancer (NSCLC).  Minimal values for detecting clinically meaningful differences were: for individual symptoms, 13.7–14.5, excluding hemoptysis (4.3); for SBI, 8.7; for Total Score, 7.2.  Patients on amrubicin experienced less deterioration in individual symptoms, less overall symptom burden, and improved QOL.  The proportions of patients with clinically relevant deterioration in coughing favored amrubicin at Cycles 2, 6, and study end (p=0.0265, p=0.0026, p=0.0194, respectively); at Cycles 2 and 6, but not study end, deterioration in dyspnea favored amrubicin (p<0.001, p=0.0419, respectively).  Similar trends favoring amrubicin were seen in the remaining symptoms. CONCLUSIONS: .  Meaningful change on the LCSS, previously developed in NSCLC, has been established here in SCLC.  Patients on amrubicin experienced less symptom deterioration during treatment.