Side effects of cancer treatment are a barrier to the care that patients can receive if the severity of the side effect forces patients to discontinue therapy. One of these side effects most often experienced by people receiving chemotherapy is neutropenia, or low count of neutrophils, which are a type of white blood cell.
However, a medication currently being investigated in clinical trial seems to successfully treat chemotherapy-induced neutropenia and may have an anti-cancer benefit too, according to Dr. Douglas Blayney, professor of medicine and associate division chief of Medical Oncology at Stanford University School of Medicine.
In an interview with CURE®, Blayney, who is also the global principal investigator for the phase 2 study of the drug, discussed the benefits of plinabulin and the risks associated with neutropenia in patients with different types of cancer.
CURE®: What type of medication is plinabulin and how does it work?
Blayney:Plinabulin is a small molecule that was isolated from bacteria and slightly modified. It was initially tested as an anti-cancer agent in lung cancer and it was discovered that plinabulin not only had an anti-cancer effect but also decreased the incidence of neutropenia — it seemed to maintain the white blood count after chemotherapy.
About five years ago, we started testing plinabulin in a clinical trial to test it against the standard of care, which is now G-CSF, or pegfilgrastim (Neulasta, Neupogen), and the potential advantage of plinabulin was that it’s given on the same day as chemotherapy and it doesn't seem to cause the bone pain that so many patients notice with G-CSF.
We’ve completed, and are in the midst of publishing, a phase 2 study with chemotherapy. We had two phase 2 studies, one is in the intermediate risk for febrile neutropenia for which pegfilgrastim is given reactively — that’s if a patient has problems with febrile neutropenia or infection after chemotherapy, and the second trial is in high febrile neutropenia risk with chemotherapy, in which pegfilgrastim is given routinely the second day after treatment. We think the phase 2 studies are intended to establish a safe and effective dose that we will carry over into the phase 3 studies.
We’re testing plinabulin primarily in the common solid tumors, so breast, lung and prostate cancers.
Are there any known side effects of Plinabulin?
It causes mild and very temporary hypertension, or high blood pressure, in the doses that we are using. But this seems to be the main side effect uncovered.
Why is it important to control neutropenia?
Neutropenia is a side effect of most of the chemotherapy drugs that we use, and it is related to the dosage. For most chemotherapy, the higher the dose, the more the incidence of neutropenia.
There's a balance with the dosing that’s in common between efficacy and the side effects. We hope that by using the standard dose of chemotherapy we can prevent neutropenia and its complications.
Neutropenia lowers the body’s ability to defend itself against bacterial infections. Sometimes these bacterial infections can lead to sepsis, shock, hypotension and even death, although that’s rare.
What phase 3 trials are currently underway?
The neutropenia trial is recruiting patients in the United States, Europe and China. And this data may be available sometime in 2020.
Plinabulin is also being tested as an anti-cancer agent. This phase 3 trial is in lung cancer testing the addition of plinabulin to lung cancer treatments, and this trial is almost complete.