Skylar Kenney, Assistant Editor

Treatment with cisplatin can result in a greater amount of hearing loss in very young children compared to the drug’s effects on older children, according to a study published in 

. Cisplatin is frequently an effective therapy for pediatric cancer, but it is also known to cause permanent hearing loss in some patients. Previous studies have found that up to 60% of children treated with cisplatin experience hearing loss.

The investigators examined data from 368 children with cancer who were treated with cisplatin and underwent audiological assessments. A total of 2052 assessments were conducted and all study participants were no longer taking cisplatin within 3 years of initiating treatment.

The study found that 75% of patients 5 years of age or younger experienced hearing loss related to treatment with cisplatin 3 years after starting the therapy, compared to 48% of patients over 5 years of age. At 3 months following the initiation of therapy, 27% of participants 5 years of age or younger had experienced cisplatin-related hearing loss, which increased to 61% at 1 year following the start of therapy.

More extreme hearing loss was associated with a higher total dose of cisplatin at 3 months, co-prescriptions of the chemotherapy drug vincristine, and a longer duration of concomitantly administered antibiotics.

“Audiological monitoring at each cycle of cisplatin treatment will allow research to advance more quickly to find the mechanistic basis of why younger children are more vulnerable to hearing loss and how best to protect hearing while being given this life-saving therapy,” said Bruce Carleton, PharmD, an investigator and director of the Pharmaceutical Outcomes Program at BC Children’s Hospital in Vancouver, British Columbia, in a press release.

The study authors note that the mechanism responsible for the higher occurrence of hearing loss in younger children is currently unknown. They suggest it is possible that maturing structures within the ear may be more susceptible to the toxicity of cisplatin, resulting in the adverse effect being more common.

In an editorial accompanying the study, Penelope Brock, MD, PD, MA, of Great Ormond Street Hospital in London, emphasized that these results offer new insights into a serious direct effect of cisplatin on children with considerable implications on the quality of life for these patients. Further, she expresses hope that this study can help initiate the process of developing a new standard of care for children receiving cisplatin.

Young children with cancer face an especially high risk of hearing loss from chemotherapy drug [news release]. EurekAlert; September 7, 2021. Accessed September 15, 2021. 

https://www.eurekalert.org/news-releases/927150

Articles

Cisplatin is frequently an effective therapy for pediatric cancer, but it is also known to cause permanent hearing loss in some patients.

Children Under 5 Years of Age Face Higher Risk of Hearing Loss Related to Cancer Drug

Apalutamide (Erleada, Johnson & Johnson) demonstrated a strong prostate-specific antigen (PSA) response and high adherence rates in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in a clinical setting, according to data presented at the virtual American Urological Association Annual Meeting (AUA 2021). 

This PSA response was also observed in a separate post-hoc analysis, which demonstrated a correlation between rapid and deep PSA response and prolonged survival for patients with either metastatic castration-sensitive prostate cancer (mCSPC) or nmCRPC.

The analysis of the phase 3 TITAN and SPARTAN studies evaluated PSA kinetics in 2259 patients with either mCSPC or nmCRPC. According to the results, patients with advanced prostate cancer treated with apalutamide in combination with androgen deprivation therapy (ADT) had significant, rapid, and durable declines in PSA in as few as 3 months following the initiation of therapy. These declines were also observed to continue beyond 1 year after the start of treatment.

“The sooner that urologists and oncologists have an indicator that a patient is benefitting from a therapy, the better able they are to provide the best care,” said Tracy McGowan, MD, therapeutic head of Prostate Cancer, US Medical Affairs at Janssen Biotech, in a press release. “As reported in this post-hoc analysis, PSA is an important early predictive indicator in patients with either mCSPC or nmCRPC, and depth and speed of PSA decline were significantly improved with apalutamide treatment.”

The percentage of patients with mCSPC who experienced a PSA decline of ≥50% or ≥90% or with an undetectable PSA (<0.2ng/mL) was approximately 3 times higher for those treated with apalutamide in combination with ADT compared to patients receiving ADT alone. No PSA decline was observed for patients with nmCRPC treated with ADT alone, but the combination therapy demonstrated a significant decline in PSA, including undetectable levels in a significant portion of patients, according to the investigators.

In the study, faster and more significant declines in PSA were correlated with an increased length of overall survival. Further, median time to deep PSA decline—defined as ≥90% from baseline and/or a PSA nadir of ≤0.2 ng/mL—was observed to be more rapid for the combination therapy of apalutamide and ADT than previously reported for other therapies.

“Outside of a clinical trial setting, health care professionals are focused on ensuring a therapy can benefit patients treated in the real world,” said Benjamin Lowentritt, MD, director of the Prostate Cancer Care Program at Chesapeake Urology, in the release “To have both high adherence rates and robust PSA reductions is very encouraging. These findings support the use of apalutamide in delaying disease progression and metastasis in patients with nmCRPC across various demographics.”

Erleada® (apalutamide) oral presentations demonstrate importance of prostate specific antigen (PSA) as key efficacy indicator and show strong patient adherence rates [news release]. Johnson & Johnson; September 11, 2021. Accessed September 15, 2021. 

https://www.jnj.com/erleada-apalutamide-oral-presentations-demonstrate-importance-of-prostate-specific-antigen-psa-as-key-efficacy-indicator-and-show-strong-patient-adherence-rates

Apalutamide (Erleada, Johnson & Johnson) demonstrated a strong prostate-specific antigen response and high adherence rates in patients with non-metastatic castration-resistant prostate cancer.

Apalutamide Demonstrates Strong PSA Response in Patients With Advanced Prostate Cancer

A phase 1, randomized, placebo-controlled clinical trial designed to study a therapeutic vaccine for opioid use disorder has enrolled its first patients, according to a press release from the University of Minnesota Medical School. Funded by a grant from the National Institutes of Health, this trial is intended to test the safety and efficacy of a vaccine designed to selectively prevent the euphoric and toxic effects of oxycodone.

The study is seeking volunteers between 18 and 59 years of age who are currently using opioids and not seeking treatment for drug use and have prior experience with intranasal opioid use. Participants are being enrolled at Columbia University in New York City and Clinilabs Drug Development Corporation in Eatontown, New Jersey, with the goal of enrolling up to 45 volunteers.

Study participants will be closely monitored for several weeks on inpatient units at Columbia University Irving Medical Center and at Clinilabs. The investigators will be following these patients to look for adverse events and determine their response to oxycodone after vaccination before shifting the study to examine their drug behavior on an outpatient basis.

“In this study, my laboratory will conduct pharmacokinetic and immunological monitoring in blood samples from immunized volunteers to ensure that they are making antibodies to oxycodone and determine whether or not the antibodies are preventing the drug from reaching the brain,” said Marco Pravetoni, PhD, an associate professor of pharmacology and medicine at the University of Minnesota Medical School, in a press release.

The vaccine being studied stimulates the body’s immune system to produce antibodies against oxycodone. In a vaccinated individual who takes oxycodone, those antibodies bind to the drug molecule and prevent it from entering the brain, which in turn would prevent the high produced by the drug, according to the researchers. Further, the vaccine’s selectivity disallows it from interfering with FDA-approved medications, such as methadone, buprenorphine, naltrexone, and naloxone.

“This medication approach is unique in that it can be used alone or in combination with other treatment medications and, importantly, may offer patients long-lasting protection against overdose if they relapse to opioid use,” said Sandra Comer, PhD, director of the Opioid Laboratory in the Division on Substance Use Disorders in the Department of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons, in the release. “The long-term goal of this program is to develop a series of opioid vaccines that target other commonly used opioids, such as heroin and fentanyl. We are very excited about this research and hope to eventually provide a safe, new treatment option for patients with opioid use disorder.”

First-in-human clinical trial for a vaccine to treat opioid use disorders enrolls first patients [news release]. EurekAlert; September 7, 2021. Accessed September 15, 2021. 

https://www.eurekalert.org/news-releases/927548

Funded by a grant from the National Institutes of Health, this trial is intended to test the safety and efficacy of a vaccine designed to selectively prevent the euphoric and toxic effects of oxycodone.

Clinical Trial Evaluating Vaccine Against Opioid Use Disorders Enrolls First Patients

Evolocumab (Repatha, Amgen) in combination with optimized statin therapy significantly improved certain features of plaque stability in patients with coronary artery disease (CAD) compared to patients receiving optimized statin therapy alone, according to data presented at ESC Congress 2021.

The investigators noted that heart attacks are often caused by the rupturing of vulnerable plaques, defined as plaques with a large lipid core with a thin fibrous cap that serves as a wall or barrier around the plaque to keep it intact. The study assessed whether evolocumab could improve plaque stability through increasing the thickness of the fibrous caps.

The randomized, double-blind, 52-week study found that the combination therapy of evolocumab and optimized statin therapy resulted in an increase of 75% in fibrous cap thickness compared to 39% on optimized statin therapy alone. Further, adding evolocumab to optimized statin therapy improved all of the study’s secondary endpoints, including a decrease in the maximum lipid arc by -57.5° compared to -31.4°.

“The majority of acute coronary syndrome events are caused by plaque rupture, and those who have had a heart attack are especially vulnerable to additional episodes of plaque rupture, demonstrating the importance of maintaining the thickness of the fibrous cap to help stabilize plaques,” said Stephen J. Nicholls, MD, PhD, professor of Cardiology and director of the Monash University Victorian Heart Institute, in a press release. “These encouraging results reaffirm the potential of Repatha and highlight the benefits of Repatha in ACS patients who initiated treatment early.”

No new safety risks were identified in the study. According to the investigators, the most common treatment-emergent adverse events were angina pectoris, myalgia, hypertension, diarrhea, fatigue, and cough. The study also demonstrated that treatment with evolocumab initiated within a week after the ACS event reduced low-density lipoprotein cholesterol by 80%, compared to 39% on statin optimization alone.

“Amgen continues to build a body of evidence to support the clinical profile of Repatha and demonstrate its benefit in patients at elevated risk of suffering another heart attack or stroke,” said David M. Reese, MD, executive vice president of Research and Development at Amgen. “This study builds on the findings from the GLAGOV study and provides evidence that low LDL-C levels can change characteristics of coronary plaque, which may explain the biology of cardiovascular event reduction we saw in the FOURIER study.”

New data at ESC Congress 2021 shows Repatha® (evolocumab) improves features of plaque stability in patients with acute coronary syndrome (ACS) [news release]. Amgen; August 27, 2021. Accessed September 2, 2021. 

https://wwwext.amgen.com/newsroom/press-releases/2021/08/new-data-at-esc-congress-2021-shows-repatha-evolocumab-improves-features-of-plaque-stability-in-patients-with-acute-coronary-syndrome-acs

The investigators noted that heart attacks are often caused by the rupturing of vulnerable plaques, defined as plaques with a large lipid core with a thin fibrous cap that serves as a wall or barrier around the plaque to keep it intact.