title: Amrubicin at a lower-dose with routine prophylactic use of granulocyte-colony stimulating factor for relapsed small-cell lung cancer.
abstract: 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/m(2) or 45 mg/m(2), 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/m(2) 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/m(2)/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/m(2) with routine prophylactic use of G-CSF may be more desirable for the treatment of relapsed SCLC in clinical practice.
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nanjo
authors.forename: Kyoko
authors.initials: K
authors.lastname: Otsuka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kida
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Higashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Tachikawa
authors.forename: Michio
authors.initials: M
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D002985:Clinical Protocols; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007970:Leukopenia / Q000209:etiology / Q000517:prevention & control; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000209:etiology / Q000517:prevention & control; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011994:Recombinant Proteins; D016019:Survival Analysis
chemical_list: D018943:Anthracyclines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C055866:amrubicin