Nitroglycerin in Non-small Cell Lung Cancer

Nitroglycerin is a nitric oxide donor which is mainly known as a vasodilating agent used in ischemic heart disease. It has also been shown to increase tumor blood flow in animal and human tumors. The addition of nitroglycerin to chemotherapy in non small cell lung cancer has been shown to generate very favorable response rates with respect to standard treatment schedules\[5\]. Theoretically nitroglycerin might reduce resistance to chemotherapy via a plethora of different effects: better tumor perfusion, direct effects of NO on cancer cells, increase in activated p53 protein and via an increased blood flow in the tumour with as consequence a higher drug concentration in the tumor \[6\] . In mice, nitric oxide donors such as isosorbide dinitrate have been shown to decrease tumor hypoxia by better tumor perfusion, which could enhance radiotherapy responses \[7\]. To date these combined effects have not been tested in humans. In this trial we would like to demonstrate the effect of nitroglycerin on tumor perfusion and hypoxia in non small cell lung cancer (using DCE and HX4 scanning), providing a rationale for further study and to test the effect of combining nitroglycerine to standard treatment of NSCLC (radiotherapy/chemotherapy).

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Non-small cell lung cancer stage IB-IV amenable for radiotherapy with curative intent.
* (Stage IV patients with oligometastic (1-4 metastases) NSCLC are regularly treated radically in the IKNL region).
* Patients not included in the PET-Boost or the Lucanix trial.
* WHO performance status 0-2.
* Willing and able to comply with the study prescriptions.
* 18 years or older.
* Ability to give and having given written informed consent before patient registration.
* No recent (\< 3 months) severe cardiac disease (NYHA class \>1) (congestive heart failure, infarction).
* No radiotherapy in 4 weeks prior to this study.
* No treatment with investigational drugs in 4 weeks prior to or during this study.
* No known allergy to nitroglycerin or nitroglycerin patch.
* No known allergy to iodine based contrast agents
* No use of Levitra, Viagra or Cialis at the time of application of the nitroglycerin patch.
* No conditions necessitating the use of ergot alkaloids, alpha blockers (eg tamsulosine), betablockers or calcium channel blockers on the day of nitroglycerin patch application).
* No other active malignancy.
* No major surgery (excluding diagnostic procedures like eg mediastinoscopy) in previous 4 weeks.
* Adequate renal function: calculated creatinine clearance at least 60ml/min.

• DERIVEDvan Elmpt W, Zegers CML, Reymen B, Even AJG, Dingemans AC, Oellers M, Wildberger JE, Mottaghy FM, Das M, Troost EGC, Lambin P. Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion. Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):240-248. doi: 10.1007/s00259-015-3169-4. Epub 2015 Sep 4. PMID 26338178