Amrubicin at a lower-dose with routine prophylactic use of granulocyte-colony stimulating factor for relapsed small-cell lung cancer

Background Recent reports have suggested the efficacy of amrubicin (AMR) for relapsed small-cell lung cancer (SCLC). However, doses of AMR in these reports were 40 mg/m2 or 45 mg/m2, and severe and frequent myelosuppression were observed. Such side effects are occasionally intolerable, as serious myelosuppression may induce fatal infections. To overcome this clinical problem, we investigated whether 35 mg/m2 of AMR administration with routine prophylactic use of granulocyte-colony stimulating factor (G-CSF) can reduce myelosuppression, while maintaining efficacy. Methods Between July 2003 and November 2008, 30 relapsed SCLC patients receiving 35 mg/m2/day of AMR were evaluated. Amrubicin was administered on days 1–3 every 3 or 4 weeks. Routine prophylactic use of G-CSF was performed beginning on day 8 and continuing for at least 5 consecutive days or until neutrophils recovered to the normal level. Results The median number of treatment cycles was four (range 1–9). No complete responses and 13 partial responses were observed, with response rates of: overall 43% (95% confidence interval [CI]: 26–63%); sensitive cases 33% (95% CI: 10–65%); and refractory cases 50% (95% CI: 26–74%) (p = 0.4651). The disease control rate (partial response and stable disease) was 80% (95% CI: 61–92%). The progression-free survival times were: overall 4.2 months (95% CI: 3.2–5.2 months); sensitive cases 4.7 months (95% CI: 2.6–5.4 months); and refractory cases 3.5 months (95% CI: 2.6–5.2 months) (p = 0.7124). The median OS times were: overall 9.6 months (95% CI: 7.2–12.5 months); sensitive cases 8.4 months (95% CI: 4.6–13.4 months); and refractory cases 11.0 months (95% CI: 6.5–12.6 months) (p = 0.9315). The 1-year survival rate was 33%. Regarding grade 3/4 hematological toxicities: leukopenia (47%); neutropenia (50%); anemia (30%); and thrombocytopenia (33%) were observed. Febrile neutropenia occurred in three patients (10%). Transfusions of red blood cells and platelets were performed for eight (27%) and one (3%) patients, respectively. Treatment-related deaths and grade 3/4 non-hematological toxicities were not observed at all. Conclusions Considering both safety and efficacy, AMR at a dose of 35 mg/m2 with routine prophylactic use of G-CSF may be more desirable for the treatment of relapsed SCLC in clinical practice.