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Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial.

ABSTRACT: Background:Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potential of nitroglycerin as a radio-sensitizer in non-small cell lung cancer (NSCLC) and the potential of functional imaging for patient selection. Material and methods:Trial NCT01210378 is a single arm phase II trial, designed to detect 15% improvement in 2-year overall survival (primary endpoint) in stage IB-IV NSCLC patients treated with radical (chemo-) radiotherapy and a Transiderm-Nitro 5 patch during radiotherapy. Patients underwent dynamic contrast-enhanced CTs (DCE-CT) and HX4 (hypoxia) PET/CTs before and after nitroglycerin. Secondary endpoints were progression-free survival, toxicity and the prognostic value of tumour perfusion/hypoxia at baseline and after nitroglycerin. Results:The trial stopped after a futility analysis after 42 patients. At median follow-up of 41 months, two-year and median OS were 58% (95% CI: 44-78%) and 38 months (95% CI: 22-54 months), respectively. Nitroglycerin could not reduce tumour hypoxia. DCE-CT parameters did not correlate with OS, whereas hypoxic tumours had a worse OS (p = 0.029). Changes in high-uptake fraction of HX4 and tumour blood flow were negatively correlated (r = -0.650, p = 0.022). The heterogeneity in treatment modalities and patient characteristics combined with a small sample size made further subgroup analysis of survival results impossible. Toxicity related to nitroglyerin was limited to headache (17%) and hypotension (2.4%). Conclusion:Nitroglycerin did not improve OS of NSCLC patients treated with (chemo-)radiotherapy. A general ability of nitroglycerin to reduce hypoxia was not shown.

SUBMITTER: Reymen BJT

PROVIDER: S-EPMC6993056 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial.

Reymen Bart J T BJT van Gisbergen Marike W MW Even Aniek J G AJG Zegers Catharina M L CML Das Marco M Vegt Erik E Wildberger Joachim E JE Mottaghy Felix M FM Yaromina Ala A Dubois Ludwig J LJ van Elmpt Wouter W De Ruysscher Dirk D Lambin Philippe P

Clinical and translational radiation oncology 20191213

<h4>Background</h4>Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potential of nitroglycerin as a radio-sensitizer in non-small cell lung cancer (NSCLC) and the potential of functional imaging for patient selection.<h4>Material and methods</h4>Trial NCT01210378 is a single arm phase II trial, designed to detect 15% improvement in 2-year overall survival (primary endpoint) in stage IB-IV NSCLC patients treated with radical (chemo- ...[more]

PMID: 32021913

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Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial.

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Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial.

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