title: A phase II study of bevacizumab with carboplatin-pemetrexed in non-squamous non-small cell lung carcinoma patients with malignant pleural effusions: North East Japan Study Group Trial NEJ013A.
abstract: Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of malignant pleural effusion (MPE). Here, a multicenter phase II trial to evaluate bevacizumab in non-squamous non-small cell lung carcinoma patients with MPE was conducted.
  
  
  
  Patients having MPE with no prior treatment and performance status of 0-2 received carboplatin (area under the curve: AUC 6; up to 6 cycles) and pemetrexed (500mg/m(2)) with bevacizumab (15mg/kg) every 3 weeks. The primary endpoint was the control rate of MPE without pleurodesis at 8 weeks after treatment. VEGF levels in plasma and MPE were measured by enzyme immunoassay.
  
  
  
  Of 30 patients entered (median 66 years; 24 males; adenocarcinoma; 4 epidermal growth factor receptor: EGFR mutations), 28 patients (2 withdrawn patients) were given a median of 4 cycles of carboplatin, and 68% of the patients received maintenance pemetrexed with bevacizumab (median 8 cycles). At eight weeks, MPE was controlled without pleurodesis in 93% of treated patients (95% confidence interval: 77-99%). At the median follow-up time of 12.8 months, 78.6% of the cases required no pleurodesis. Response rate was 46%, and median progression-free survival (PFS) and overall survival (OS) were 8.2 months and 18.6 months, respectively. Toxicities of grade ≥3 included neutropenia (28.6%), thrombocytopenia (28.6%), proteinuria (3.6%), and hypertension (3.6%). Assessment of VEGF levels before treatment indicated that patients with low VEGF (<1000pg/ml) in MPE frequently needed pleurodesis (p=0.011), and that high VEGF (≥100pg/ml) in plasma was indicative of poor prognosis in the context of PFS (p=0.012).
  
  
  
  The combination of bevacizumab with carboplatin and pemetrexed demonstrated efficacy with acceptable toxicities in patients with MPE.
authors: Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa, Tokyo, Japan. Electronic address: usui@east.ntt.co.jp.
authors: Kazuhiro
authors: K
authors: Usui
authors: Department of Pulmonary Medicine, Sendai Kousei Hospital, Japan.
authors: Shunichi
authors: S
authors: Sugawara
authors: Department of Respiratory Medicine, Ishikawa Prefectural Central Hospital, Japan.
authors: Masaru
authors: M
authors: Nishitsuji
authors: Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Japan.
authors: Yuka
authors: Y
authors: Fujita
authors: Department of Respiratory Medicine, Tohoku University Hospital, Japan.
authors: Akira
authors: A
authors: Inoue
authors: Department of Pulmonology, National Hospital Organization Disaster Medical Center, Japan.
authors: Atsuto
authors: A
authors: Mouri
authors: Department of Respiratory medicine, Saka General Hospital, Japan.
authors: Hiroshi
authors: H
authors: Watanabe
authors: Department of Thoracic Oncology, Saitama Cancer Center, Japan.
authors: Hiroshi
authors: H
authors: Sakai
authors: Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Japan.
authors: Ichiro
authors: I
authors: Kinoshita
authors: Department of Medical Oncology, KKR Sapporo Medical Center, Japan.
authors: Yoshihito
authors: Y
authors: Ohhara
authors: Department of Respiratory Medicine, Miyagi Cancer Center, Japan.
authors: Makoto
authors: M
authors: Maemondo
authors: Department of Respiratory Medicine and Infectious Disease, Niigata University Medical and Dental Hospital, Japan.
authors: Hiroshi
authors: H
authors: Kagamu
authors: Department of Comprehensive Medicine 1, Saitama Medical Center Jichi University, Japan.
authors: Koichi
authors: K
authors: Hagiwara
authors: Department of Respiratory medicine, Saitama International Medical Center, Saitama Medical University, Japan.
authors: Kunihiko
authors: K
authors: Kobayashi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019233:Retreatment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000068437:Pemetrexed; D000068258:Bevacizumab; D016190:Carboplatin; D066246:ErbB Receptors
keywords: Bevacizumab; Lung cancer; Malignant pleural effusions; Non-small cell lung cancer; Pemetrexed; Pleurodesis