title: A multicenter phase II trial of S-1 combined with bevacizumab after platinum-based chemotherapy in patients with advanced non-squamous non-small cell lung cancer.
abstract: OBJECTIVE
  This phase II trial investigated the efficacy and safety of S-1 plus bevacizumab (SB) after failure of platinum-based chemotherapy in patients with non-squamous non-small cell lung cancer (non-sq NSCLC).
  
  
  METHODS
  Patients with non-sq NSCLC who had undergone prior platinum-based chemotherapy, regardless of the use of bevacizumab, were eligible. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, and bevacizumab (15 mg/kg) on day 1 every 3 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  Twenty-eight patients (14 males and 14 females; median age 62 years; performance status 0/1/2: 21/7/0) were accrued from 4 centers. Almost half (n = 15, 53.6 %) of these had received prior bevacizumab therapy. The median PFS and overall survival were 3.2 months [95 % confidence interval (CI) 2.2-4.0 months] and 11.4 months (95 % CI 8.9-13.9 months), respectively. Prior exposure to bevacizumab did not affect the PFS. An objective response was observed in 4 patients, the response rate and disease control rate being 14.3 and 85.7 %, respectively. The treatment was well tolerated, the most common treatment-related side effects being anorexia (75 %) and fatigue (68 %).
  
  
  CONCLUSIONS
  Although SB was well tolerated, this combination did not provide any additional benefit in terms of PFS for patients with non-sq NSCLC after failure of platinum-based chemotherapy. It will be important to clarify the most suitable agent for use with bevacizumab, and the optimal timing of bevacizumab therapy for lung cancer.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan. kayamada@med.kurume-u.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Respirology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ichiki
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hisamatsu
authors.affiliation: Department of Respirology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeoka
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Shukuya
authors.affiliation: Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tokito
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D017671:Platinum Compounds / Q000008:administration & dosage; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D017671:Platinum Compounds; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid
keywords: Bevacizumab; Non-small cell lung cancer; Non-squamous; S-1