BACKGROUND: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. RESULTS: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). CONCLUSIONS: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings.
BACKGROUND:Nitroglycerin, a nitric oxidedonor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: This is a phase II trial of locally advanced NSCLCpatients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. RESULTS: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). CONCLUSIONS: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings.
Authors: Catharina M L Zegers; Wouter van Elmpt; Bart Reymen; Aniek J G Even; Esther G C Troost; Michel C Ollers; Frank J P Hoebers; Ruud M A Houben; Jonas Eriksson; Albert D Windhorst; Felix M Mottaghy; Dirk De Ruysscher; Philippe Lambin Journal: Clin Cancer Res Date: 2014-10-14 Impact factor: 12.531
Authors: Jan Scicinski; Bryan Oronsky; Shoucheng Ning; Susan Knox; Donna Peehl; Michelle M Kim; Peter Langecker; Gary Fanger Journal: Redox Biol Date: 2015-07-02 Impact factor: 11.799
Authors: Bart J T Reymen; Marike W van Gisbergen; Aniek J G Even; Catharina M L Zegers; Marco Das; Erik Vegt; Joachim E Wildberger; Felix M Mottaghy; Ala Yaromina; Ludwig J Dubois; Wouter van Elmpt; Dirk De Ruysscher; Philippe Lambin Journal: Clin Transl Radiat Oncol Date: 2019-12-13