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Inhaled iloprost may prevent cancer progression among former smokers
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A trial at University of Colorado Cancer Center is designed to evaluate the potential of an inhaled form of the pulmonary hypertension drug iloprost to heal lung damage among former smokers and prevent progression to cancer.
Robert L. Keith, MD, professor of medicine in the division of pulmonary sciences and critical care medicine at University of Colorado Denver, and colleagues have conducted chemoprevention clinical trials at Denver VA Medical Center and University of Colorado Hospital since the 1990s.
Multiple preclinical models have shown iloprost slows the formation of lung cancers, including those exposed to tobacco smoke.
For their ongoing trial, Keith and colleagues will randomly assign a cohort of former smokers to placebo or four daily at-home inhalation treatments of iloprost. Researchers hope to have data from this trial in early 2018.
HemOnc Today spoke with Keith about the trial, the theory behind the mechanism of action and the potential implications if iloprost is successful in this setting.
Question: What prompted this trial?
Answer: Our group at University of Colorado Denver has had a long interest in the chemoprevention of lung cancer, and we have done a lot of work with prostacyclin. We have shown in many preclinical models that it blocks the development of lung cancer, both with chemicals or with tobacco smoke.
Q: How is the trial being conducted?
A: We know from previous research that if someone has damage in the airways, and if the damage persists over time, they are at increased risk for squamous cell lung cancer. This trial is using inhaled iloprost. Earlier trials included oral iloprost, and I am hoping that we will soon be able to conduct another trial with the oral agent, but most of these agents have transitioned to inhalational administration. In some ways, this is even more attractive because, if we deliver the medication by inhaler or nebulizer, we are getting the agent directly where we want it — right to the airways. With this ongoing trial, we are recruiting former smokers with a similar history of tobacco use, age and abnormal cells in their sputum. Of note, participants must have quit smoking for at least 1 year. I tell all of my patients that this is the first step to prevent lung cancer, and that chemoprevention can be viewed in specific stages. Stage one is to quit smoking. Stage two is to identify at-risk lesions. Stage 3 is to use medications or other interventions to prevent cancer from developing.
Q: Can you talk about the potential mechanism of action?
A : We are still determining the exact mechanism with our ongoing study. If cancer cells are exposed to iloprost, cancer cell growth is not affected. We, therefore, think that iloprost is an agent that may work selectively on precancerous cells and affects the microenvironment. Our group has shown that, if we expose cells grown from biopsies to iloprost, they can revert to a more normal appearance and function. Prostaglandins like iloprost have many anti-inflammatory effects, so the effects may be focused on the premalignant microenvironment and the immune response. We are working hard to figure out how this works, because it might be an even better chemopreventive agent than we previously thought.
Q: What are the potential implications if it is successful?
A: Although we have made advances in lung cancer treatment, the 5-year survival is still quite poor compared with other cancer types. The 5-year survival for lung cancer is approximately 18%. Much of the disease is diagnosed at a later stage and it is, therefore, hard to have curative therapy. There is controlling therapy, but not necessarily curative therapy. We now screen for lung cancer, and screening means we will pick up earlier-stage lung cancers and will have more long-term survivors. However, more survivors means we will have more people at risk for a second lung cancer. This might be an excellent and motivated group to tell that we [may be able to] prevent the potential for a subsequent lung cancer. These agents also have a role in treating certain lung diseases, such as pulmonary hypertension. The ideal preventive agent would treat diseases commonly found in patients with lung cancer, such as chronic obstructive pulmonary disease, and prevent lung cancer.
Q: When might the data from this trial become available?
A: We hope to have data available in early 2018. The next cohort will be dosed twice daily. We eventually hope to conduct a larger trial with either oral or inhaled iloprost.
Q: Is there anything else that you would like to mention?
A: I want to thank the patient volunteers and our entire group that conducts these trials. Prevention is incredibly important, and I think that — for lung cancer, which has the poorest survival — we may be able to make some of the biggest advances if we can find effective preventive agents to affect cancer from developing in those that have successfully quit smoking. – by Jennifer Southall
For more information:
Robert L. Keith, MD, can be reached at University of Colorado Denver, 1250 14th St., Denver, CO 80217; email: robert.keith@ucdenver.edu.
Disclosure: Keith reports no relevant financial disclosures.