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)

Lung Cancer. 2015 Apr;88(1):57-62. doi: 10.1016/j.lungcan.2015.01.012. Epub 2015 Jan 23.

Abstract

Objectives: 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.

Patients and 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00620971.

Keywords: Bevacizumab; Cisplatin; NSCLC; Overall response rate; Sequential treatment; Vinorelbine.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Docetaxel
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Bevacizumab
  • Vinblastine
  • Cisplatin
  • Vinorelbine
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00620971