Repurposing angina pectoris medication as lung cancer treatment
Nitroglycerin as a sensitiser in the treatment of non-small cell lung cancer: a phase II trial.
Funding
Why this trial
Lung cancer is still one of the most common cancers, with non-small cell lung cancer the most frequently occurring subtype. The treatment of non-small lung cancer is difficult, as tumours often do not respond sufficiently to available treatments. One of the reasons for this may be a lack of oxygen in the tumour. Tumours, due to their rapid growth, often do not have enough time to develop a sufficient blood supply system. This causes a lack of oxygen, which is required for radiotherapy to be effective. A better blood supply in the tumour could increase oxygen levels and sensitise the cancer cells to radiotherapy. One of the drugs that can be used to increase the blood supply in tissues is nitroglycerin.
Further research is needed to validate this hypothesis. The effect of nitroglycerin on radiation therapy in patients has not been studied in depth.
Why this intervention
Nitroglycerin has been on the market for to improve blood flow after a heart attack. It is a safe, effective and cheap drug with a low level of side effects. Previous research in animals has shown that the use of nitroglycerin can enhance sensitivity to radiation and chemotherapy in cancer by increasing the tumour blood flow.
If it was shown that nitroglycerin could improve survival by enhancing the effect of radiotherapy, this could be a safe, effective and low-cost lung cancer treatment.
Trial design
To study the effect of nitroglycerin in non-small cell lung cancer on survival, 60 patients were enrolled in this single centre non-randomized phase II trial. All patients were given nitroglycerin patches during their radiotherapy treatment. The effect of nitroglycerin on the blood supply and oxygen levels in the tumours was measured.
Results
The trial was closed after 47 patients had been enrolled because an intermediate analysis found that nitroglycerin was unlikely to increase survival of lung cancer patients. The final results show that adding nitroglycerin to radiotherapy in non-small cell lung cancer did not improve survival compared to what would have been expected without nitroglycerin. Nitroglycerin patches were well tolerated. Also, nitroglycerin did not modify the oxygen level in the tumors, which was the initial hypothesis made by the researchers. Overall, nitroglycerin is not considered a good sensitizer to radiotherapy in patients with non-small cell lung cancer.
The results have been published in the scientific journal Clinical and Translational Radiation Oncology (January 2020).
Partners
Researchers:
- Prof. Philippe Lambin, University Hospital Maastricht/MAASTRO Clinic, Maastricht, The Netherlands (Principal Investigator)
- Dr. Bart Reymen, University Hospital Maastricht/MAASTRO Clinic, The Netherlands (Trial Coordinator)
Sponsor:
- MAASTRO Clinic, Maastricht, The Netherlands
Our role
Why we support this trial
Intervention has little or no commercial value
Expected survival benefit
No major hurdle for clinical implementation
Funding
References
More info on clinicaltrials.gov: NCT01210378
Jordan, B.F., et al. (2000). Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI. Int J Radiat Oncol Biol Phys, 48(2), 565-570. doi:10.1016/S0360-3016(00)00694-5
Konovalova N.P., et al. (2003). Nitric oxide donor increases the efficiency of cytostatic therapy and retards the development of drug resistance. Nitric Oxide, 8(1), 59-64. doi:10.1016/S1089-8603(02)00142-8
Ng, Q.S., et al. (2006). Lung cancer perfusion at multi-detector row CT: reproducibility of whole tumor quantitative measurements. Radiology, 239(2), 547-553. doi:10.1148/radiol.2392050568
Yasuda, H., et al. (2006). Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma. Clin Cancer Res, 12(22), 6748-6757. doi:10.1158/1078-0432.CCR-06-1124
Yasuda, H., et al. (2006). Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small-cell lung cancer. J Clin Oncol, 24(4):688-694. doi:10.1200/JCO.2005.04.0436
Last updated: March 2024.