Tag: prostate cancer

Researchers have identified an investigational therapeutic approach that could be effective against treatment-resistant prostate cancer. Results of the Phase II clinical trial performed by Cedars-Sinai Cancer investigators and published in Molecular Therapy, have led to a larger, multicentre trial that will soon be underway.

Cancer of the prostate is the second-leading cause of cancer-related death in men. Many prostate tumours are not aggressive and may require no or minimal treatment. Aggressive tumours are initially treated with surgery or radiation therapy.

In roughly a third of patients, the cancer comes back after initial treatment, said Neil Bhowmick, PhD, research scientist at Cedars-Sinai Cancer, professor of Medicine and Biomedical Sciences and senior author of the study. Those patients are usually treated with medications that suppress the actions of testosterone and other androgens, which promote prostate tumour growth.

“Patients do really well until the tumour figures a way around the androgen-suppressing therapy,” Bhowmick said. “One way that it can do this is to cause cells to make only part of the protein that the drug binds to, rendering the drug useless. The partial proteins are called splice variants.”

Through research with human cells and laboratory mice, study first author Bethany Smith, PhD, figured out that the cancer cells were using a protein called CD105 to signal to the surrounding supportive cells to make these slice variant proteins. Investigators then conducted a trial in human patients to test a drug that they hoped would keep those partial proteins from forming by inhibiting CD105.

In the trial, 9 patients whose tumours were resistant to androgen-blocking therapy continued that therapy but were also given a CD105 inhibitor called carotuximab. Forty percent of those patients experienced progression-free survival, based on radiographic imaging.

“Every single one of the patients in our trial was totally resistant to at least one androgen suppressor, and the normal course of action would be to simply try a different one or chemotherapy, which research has shown generally doesn’t stop tumor growth for more than about three months,” Bhowmick said. “Carotuximab prevented the cancer’s workaround and made the tumor sensitive to androgen-suppressing therapy.”

Importantly, Bhowmick said, carotuximab also appears to prevent androgen receptor splice variants in the supporting cells surrounding tumours, further sensitising the tumour to the androgen suppressor.

“We found that this therapy may be able to, especially in early cancers, resensitize select patients to androgen suppression. This could allow patients to avoid or delay more toxic interventions such as cytotoxic chemotherapy,” said Edwin Posadas, MD, associate professor of Medicine at Cedars-Sinai and a co-author of the study. “We also hope to find ways of predicting which patients are most likely to benefit from this approach by testing blood and tissue samples using next-generation technologies housed at Cedars-Sinai Cancer.”

Study co-author Sungyong You, PhD, director of the Urologic Oncology Bioinformatics Group, pinpointed three biomarkers that could help indicate which patients will respond to this investigational therapy, and the team will validate those markers in a new clinical trial. This will allow future studies to target patients most likely to be helped by this intervention, Bhowmick said.

Source: Cedars-Sinai Medical Center

Men taking abiraterone or enzalutamide, two common oral medications for advanced prostate cancer in combination with hormone therapy, were at greater risk of serious metabolic or cardiovascular issues than patients receiving hormone therapy alone.

Patients taking abiraterone, an androgen biosynthesis inhibitor, had 1.77 greater risk of emergency room or the hospital admission due to diabetes, hypertension or heart disease compared to those who were only on hormone therapy. The risk was 1.22 for those receiving enzalutamide.

Compared to patients not receiving abiraterone, those taking abiraterone were also more likely to need an outpatient visit with their physician related to at least one of these health conditions. That was not the case if the man was taking enzalutamide.

Abiraterone and enzalutamide were both found to be relatively safe in clinical trials, but concerns that the population of patients who participated in the trials was different than those in real-life settings prompted the researchers to take another look at the effects of the drugs.

For instance, this research exclusively analysed patients with Medicare health insurance, and the majority of men studied were significantly older than those in the drugs’ clinical trials.

“Patients enrolled in clinical trials tend to be highly selected and often times do not reflect the patient population in day-to-day practice,” said first author Lillian Y. Lai, MD, MS, at Michigan Medicine. “Trial participants also undergo stringent safety evaluations that some of our patients do not have access to. By studying adverse events in real-life settings, we can better understand the risks of these life-prolonging cancer treatments and help clinicians and patients make informed decisions regarding treatment.”

Since metabolic and cardiovascular conditions tend to be under the purview of primary care providers, Dr Lai and her fellow authors recommend team-based care that involves PCPs for patients with advanced prostate cancer as a way to manage these higher risks.

“With continued expansion of the indications for abiraterone and enzalutamide to earlier stages of the disease, increasing numbers of men will be receiving these therapies for longer periods of time,” Dr Lai said. “This will potentially amplify the scope of men affected and increase the magnitude of the risks of adverse events, making careful attention to management of these issues crucial.”

Source: University of Michigan