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Type: Journal article
Title: A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)
Author: Dingemans, A.
Groen, H.
Herder, G.
Stigt, J.
Smit, E.
Bahce, I.
Burgers, J.
van den Borne, B.
Biesma, B.
Vincent, A.
van der Noort, V.
Aerts, J.
Citation: Annals of Oncology, 2015; 26(11):2286-2293
Publisher: Oxford Academic
Issue Date: 2015
ISSN: 0923-7534
Statement of
A.-M. C. Dingemans, H. J. M. Groen, G. J. M. Herder, J. A. Stigt, E. F. Smit, I. Bahce, J. A. Burgers, B. E. E. M. van den Borne, B. Biesma, A. Vincent, V. van der Noort, J. G. Aerts on behalf of the NVALT study group
Abstract: Background: Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. Patients and methods: In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)–paclitaxel (200 mg/m2)–bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day −2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. Results: Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6–7.3) and 5.1 months (4.2–5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96–1.67). Overall survival (OS) was 11.6 months (8.8–13.6) in control arm and 9.4 months (7.8–11.3) in experimental arm, HR 1.02 (95% CI 0.71–1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). Conclusion: Adding NTG to first-line carboplatin–paclitaxel–bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC.
Keywords: Nonsmall-cell lung cancer; nitroglycerin; bevacizumab; VEGF
Rights: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
DOI: 10.1093/annonc/mdv370
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