title: Pilot phase II study of metronomic chemotherapy in combination with bevacizumab in patients with advanced non-squamous non-small cell lung cancer.
abstract: The goal of this study was to explore the efficacy and tolerability of metronomic chemotherapy, a novel anti-angiogenic treatment strategy, in combination with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  
  Subjects with newly diagnosed stage IV NSCLC were treated with 4-week cycles of paclitaxel 80mg/m2and gemcitabine 300mg/m2weekly for three weeks, plus bevacizumab 10mg/kg every two weeks. Radiologic assessments were performed every 8 weeks. The primary endpoint was progression free survival (PFS). An exploratory objective was to correlate plasma levels of angiogenic biomarkers with treatment response.
  
  
  
  Thirty-nine subjects were included in the intent to treat (ITT) analysis. The objective response rate (ORR) was 56%, the median PFS was 8.5 months, and median overall survival (OS) was 25.5 months. The PFS rate at 6, 12, and 24 months was 61%, 21%, and 11% respectively. The OS rate at 12 and 24 months was 74% and 53% respectively. Treatment was well tolerated, without significant myelosuppressive, gastrointestinal, or neurologic events. Subjects with less than median baseline values of angiopoietin-2 and IL-8 experienced significantly longer PFS. Longer OS was associated with subjects with less than the median baseline values for PLGF and angiopoietin-2. There were statistically significant differences in median values of several biomarkers between cycles 1 and 3 in subjects with objective responses.
  
  
  
  The combination of paclitaxel and gemcitabine, delivered in a metronomic schedule, in combination with bevacizumab, appears to be an effective and tolerable treatment strategy in patients with advanced NSCLC.
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Jones
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Mary S
authors.initials: MS
authors.lastname: Jerome
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Deborah
authors.initials: D
authors.lastname: Miley
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Bradford E
authors.initials: BE
authors.lastname: Jackson
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Mollie R
authors.initials: MR
authors.lastname: DeShazo
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Vishnu V B
authors.initials: VV
authors.lastname: Reddy
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Karan P
authors.initials: KP
authors.lastname: Singh
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States.
authors.forename: Olivia C
authors.initials: OC
authors.lastname: Brown
authors.affiliation: Division of Hematology/Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Preventive Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States; Division of Laboratory Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, United States. Electronic address: pacorobertuab@cs.com.
authors.forename: Francisco
authors.initials: F
authors.lastname: Robert
mesh_terms: D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage / Q000494:pharmacology*; D054316:Biomarkers, Pharmacological / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination / Q000379:methods*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D054316:Biomarkers, Pharmacological; D003841:Deoxycytidine; D000068258:Bevacizumab; D017239:Paclitaxel; D000093542:Gemcitabine
keywords: Bevacizumab; Metronomic chemotherapy; Non-small cell lung cancer