title: Phase I/II study of amrubicin and nedaplatin in patients with untreated, advanced, non-small cell lung cancer.
abstract: A phase I/II study of combination chemotherapy with amrubicin and nedaplatin for patients with untreated, advanced, non-small cell lung cancer (NSCLC) was conducted. Amrubicin was given on days 1-3, with nedaplatin given on day 1. The treatment was repeated every 3 weeks. In the phase I trial, the initial amrubicin dose of 25 mg/m(2) was escalated in 5-mg/m(2) increments until the maximum tolerated dose was reached, with the dose of nedaplatin fixed at 100 mg/m(2). In the phase II trial, the primary endpoint was the overall response rate (ORR), assuming 20% for a standard therapy and 40% for a target therapy (α = 0.05 and β = 0.20), and the estimated required total number of patients was 35. In the phase I study, nedaplatin 100 mg/m(2) and amrubicin 25 mg/m(2) was recommended. In the phase II study, 17 out of 35 patients achieved a partial response, and the ORR was 48.6%. Grade 3/4 neutropenia, grade 3 anemia and grade 3/4 thrombocytopenia occurred in 62.9, 11.4 and 11.4% of cycles, respectively. Febrile neutropenia occurred in 5 cycles (3.9%) and all cases were manageable. The recommended dose of this combination is well tolerated and effective in patients with advanced NSCLC.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Hospital; Unit of Molecular Microbiology and Immunology, Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Ogawara
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Katsumi
authors.initials: K
authors.lastname: Nakatomi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Kohei
authors.initials: K
authors.lastname: Motoshima
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mizoguchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakano
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Takemoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Gyotoku
authors.forename: Seiji
authors.initials: S
authors.lastname: Nagashima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D009944:Organoplatinum Compounds; C053989:nedaplatin; C055866:amrubicin