Paclitaxel-Carboplatin-Bevacizumab +/- Nitroglycerin in Metastatic Non-Squamous-Non-Small Cell Lung Cancer

Summary

This study is designed to assess the effects of adding nitroglycerin (NTG) patches, delivery 25 mg NTG per 24 h, to the standard first line treatment of metastatic non-squamous non-small cell lung cancer (NSCLC), i.e. 4 cycles of carboplatin-paclitaxel-bevacizumab, followed by bevacizumab alone until disease progression. Tumor hypoxia is a common phenomenon in lung cancer; it is a known poor prognostic marker, related to treatment resistance. Pre-clinical studies have shown that nitric oxide (NO) donating drugs may decrease hypoxia related drug resistance. NTG is a NO donating drug. NTG increases tumor blood flow and thereby augments antitumor drug delivery to the tumor. A randomized phase II has shown an increase in the response rate from 42% to 72%, when NTG patches (25 mg/day, day -2 to +3) were added to vinorelbine/cisplatin in patients with advanced NSCLC. In addition, the time to progression increased from 185 to 327 days. The hypothesis of the present study is that adding NTG transdermal patches to bevacizumab containing chemotherapy improves progression free survival, response rate and overall survival in patients with metastatic non-squamous NSCLC.

Timeline

Start

2011-01

Primary completion

2014-06

Completion

2020-08

Publications

• Results Dingemans AM, Groen HJ, Herder GJ, Stigt JA, Smit EF, Bahce I, Burgers JA, van den Borne BE, Biesma B, Vincent A, van der Noort V, Aerts JG; NVALT study group. 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)dagger. Ann Oncol. 2015 Nov;26(11):2286-93. doi: 10.1093/annonc/mdv370. Epub 2015 Sep 7.
• Results de Jong EE, van Elmpt W, Leijenaar RT, Hoekstra OS, Groen HJ, Smit EF, Boellaard R, van der Noort V, Troost EG, Lambin P, Dingemans AC. [18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches. Eur J Nucl Med Mol Imaging. 2017 Jan;44(1):8-16. doi: 10.1007/s00259-016-3498-y. Epub 2016 Sep 6.
• Results Degens JHRJ, Sanders KJC, de Jong EEC, Groen HJM, Smit EF, Aerts JG, Schols AMWJ, Dingemans AC. The prognostic value of early onset, CT derived loss of muscle and adipose tissue during chemotherapy in metastatic non-small cell lung cancer. Lung Cancer. 2019 Jul;133:130-135. doi: 10.1016/j.lungcan.2019.05.021. Epub 2019 May 20.
• Results de Goeje PL, Poncin M, Bezemer K, Kaijen-Lambers MEH, Groen HJM, Smit EF, Dingemans AC, Kunert A, Hendriks RW, Aerts JGJV. Induction of Peripheral Effector CD8 T-cell Proliferation by Combination of Paclitaxel, Carboplatin, and Bevacizumab in Non-small Cell Lung Cancer Patients. Clin Cancer Res. 2019 Apr 1;25(7):2219-2227. doi: 10.1158/1078-0432.CCR-18-2243. Epub 2019 Jan 14.
• de Jong EEC, Hendriks LEL, van Elmpt W, Gietema HA, Hofman PAM, De Ruysscher DKM, Dingemans AC. What you see is (not) what you get: tools for a non-radiologist to evaluate image quality in lung cancer. Lung Cancer. 2018 Sep;123:112-115. doi: 10.1016/j.lungcan.2018.07.014. Epub 2018 Jul 18.

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