title: Phase I trial of irinotecan and amrubicin with granulocyte colony-stimulating factor support in extensive-stage small-cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor, with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support to overcome the neutropenia associated with this particular combination. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 and the dose-limiting toxicities (DLTs) of this combination in extensive-stage small-cell lung cancer (ED-SCLC) patients.
  
  
  METHODS
  Fifteen patients with ED-SCLC were treated at 3-week intervals with amrubicin on days 1-3 plus 60 mg/m(2) CPT-11 on days 1 and 8. In addition, prophylactic rhG-CSF (50 μg/m(2)) was given from day 4 to day 21, except on the day of CPT-11 administration. Amrubicin was started at 30 mg/m(2) and then escalated in 5 mg/m(2) increments until MTD was reached.
  
  
  RESULTS
  The MTD of amrubicin was 35 mg/m(2), since 2 of 4 patients experienced DLTs during the first cycle of treatment at the 40 mg/m(2) dose level. Neutropenia, neutropenic fever, ileus, and diarrhea were the DLTs. There were 13 partial responses among the 13 assessable patients, yielding an overall response rate of 100 %. Median progression-free survival and overall survival were 7.4 months and 13.4 months, respectively.
  
  
  CONCLUSIONS
  The combination of amrubicin and CPT-11 showed high activity against ED-SCLC with acceptable toxicity. Use of rhG-CSF allowed the dose of amrubicin to be raised 40 % above that in the original regimen (60 mg/m(2) CPT-11 and 25 mg/m(2) amrubicin).
authors.affiliation: Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato Minami-Ku, Sagamihara Kanagawa, 252-0374, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Asakuma
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Mayuko
authors.initials: M
authors.lastname: Wada
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ryuge
authors.forename: Ken
authors.initials: K
authors.lastname: Katono
authors.forename: Masanori
authors.initials: M
authors.lastname: Yokoba
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fukui
authors.forename: Akira
authors.initials: A
authors.lastname: Takakura
authors.forename: Sakiko
authors.initials: S
authors.lastname: Otani
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Maki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Igawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yanaihara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mitsufuji
authors.forename: Masaru
authors.initials: M
authors.lastname: Kubota
authors.forename: Masato
authors.initials: M
authors.lastname: Katagiri
authors.forename: Jiichiro
authors.initials: J
authors.lastname: Sasaki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000077146:Irinotecan; C055866:amrubicin; D002166:Camptothecin