title: Sequential administration of vinorelbine plus cisplatin and bevacizumab followed by docetaxel plus gemcitabine and bevacizumab compared to docetaxel plus cisplatin and bevacizumab regimen as first-line therapy for advanced or metastatic non-squamous non-small cell lung cancer: A multicenter randomized phase II trial of the Hellenic Oncology Research Group (HORG).
abstract: OBJECTIVE
  To compare the activity and tolerance of the consecutive administration of four active chemotherapeutic agents in combination with bevacizumab to a bevacizumab- and platinum-based chemotherapy doublet as front-line treatment in patients with non-squamous NSCLC.
  
  
  METHODS
  Patients with advanced/metastatic NSCLC, performance status of 0-2 and normal organ function were randomized to receive either 3 cycles every 3 weeks of cisplatin 80 mg/m(2) (day 1), oral vinorelbine 60 mg/m(2) (days 1 and 8) and bevacizumab 15 mg/kg (day 1) every 3 weeks (VCB regimen) followed by 3 cycles of docetaxel (75 mg/m(2), day 1), gemcitabine (1100 mg/m(2), days 1 and 8) and bevacizumab 15 mg/kg (day 1) (DGB regimen) (arm A) or 6 cycles of cisplatin 80 mg/m(2), docetaxel 75 mg/m(2) and bevacizumab 15 mg/kg on day 1 (DCB regimen; arm B) every 3 weeks.
  
  
  RESULTS
  Thirty-eight and 39 patients were enrolled in arm A and B, respectively. The study did not meet its primary endpoint since, the ORR was 39.5% (95% CI: 23.9-55.0%; 1CR and 14 PR) and 46.2% (95% CI: 30.5-61.8%; 2 CR and 16 PR) in arm A and B, respectively (p=0.554). There was no significant difference in terms of response duration (7.4 versus 4.7 months in arm A and B, respectively; p=0.697), progression-free survival (5.8 versus 5.5 months, respectively; p=0.540) and overall survival (16.9 versus 10.9 months; p=0.390). No difference was recorded between the two arms regarding the toxicity profile. There were two drug-related deaths in arm B.
  
  
  CONCLUSIONS
  Sequential therapy of VCB followed by DGB is a feasible and well-tolerated regimen but failed to show any superiority over the standard DCB regimen.
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece. Electronic address: thankotsakis@hotmail.com.
authors: A
authors: A
authors: Kotsakis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: N
authors: N
authors: Kentepozidis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: Ch
authors: Ch
authors: Emmanouilidis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: A
authors: A
authors: Polyzos
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: A
authors: A
authors: Agelidou
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: M
authors: M
authors: Vaslamatzis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: V
authors: V
authors: Chandrinos
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: S
authors: S
authors: Agelaki
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: L
authors: L
authors: Vamvakas
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: K
authors: K
authors: Kalbakis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: P
authors: P
authors: Katsaounis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: D
authors: D
authors: Stoltidis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: G
authors: G
authors: Nintos
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: D
authors: D
authors: Hatzidaki
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: E K
authors: EK
authors: Vetsika
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: D
authors: D
authors: Mavroudis
authors: On behalf of the Lung Cancer Working Group of the Hellenic Oncology Research Group (HORG), 55 Lomvardou Street, 11471, Athens, Greece.
authors: V
authors: V
authors: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000068258:Bevacizumab; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine
keywords: Bevacizumab; Cisplatin; NSCLC; Overall response rate; Sequential treatment; Vinorelbine