title: A randomized phase II study of bevacizumab in combination with docetaxel or S-1 in patients with non-squamous non-small-cell lung cancer previously treated with platinum based chemotherapy (HANSHIN Oncology Group 0110).
abstract: OBJECTIVE
  This randomized phase II trial investigated the efficacy and safety of docetaxel plus bevacizumab and S-1 plus bevacizumab in the second-line treatment of non-squamous (non-Sq) non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with non-Sq NSCLC who experienced disease progression after prior platinum-based chemotherapy with or without bevacizumab were randomly assigned to receive docetaxel plus bevacizumab (DB) once every 3 weeks or S-1 orally twice daily on days 1-14 plus bevacizumab (SB) on day 1 every 3 weeks until disease progression.
  
  
  RESULTS
  Ninety patients were randomized. The median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]=3.0-6.5) in DB and 3.5 months (95% CI=2.9-5.9) in SB. The objective response rate was significantly higher in DB than in SB (22.2% vs. 2.2%; P=0.004), whereas the disease control rates of the arms were identical (62.2% vs. 62.2%; P=1.00). Patients receiving DB were more likely to have ≥grade 3 neutropenia (93.4% vs. 4.4%) and febrile neutropenia (33.3% vs. 0%) than SB. In DB, PFS and overall survival (OS) were significantly longer among bevacizumab-naïve patients than among bevacizumab-experienced patients (median PFS: 7.2 vs. 2.9 months; P=0.004; and median OS: 21.3 vs. 14.1 months; P=0.012).
  
  
  CONCLUSIONS
  DB and SB produced modest PFS benefits in the second-line treatment of patients with advanced non-Sq NSCLC. Because of the toxicity of DB and the low response rate of SB, neither regimen warrants further investigation, excluding DB in bevacizumab-naïve patients with advanced non-Sq NSCLC.
authors.affiliation: Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan. Electronic address: nishinishipptruth@yahoo.co.jp.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nishino
authors.affiliation: Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Imamura
authors.affiliation: Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima Minamimachi Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima Minamimachi Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima Minamimachi Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Okuda
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Urata
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Yosihihiro
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Tachihara
authors.affiliation: Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
authors.forename: Souichirou
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Department of Respiratory Medicine, Kobe City Medical Center, West Hospital, Kobe, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kaneda
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Medical Oncology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077143:Docetaxel; D004338:Drug Combinations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D010984:Platinum / Q000008:administration & dosage; D019233:Retreatment; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D000068258:Bevacizumab; D010984:Platinum; D010094:Oxonic Acid
keywords: Bevacizumab; Docetaxel; Non-squamous non-small-cell lung cancer; Phase II; S-1; Second-line