The phase 3 study, published online in The Lancet, is the latest to show the effectiveness
of everolimus in slowing the cell growth that is overactive in patients with TSC.
In testing on two mouse cell lines, the drug combination reduced the viability of cancer cells by about 50 percent when compared
with everolimus alone, according to the findings.
One idea was finding something to make the antitumor
drug everolimus more effective.
Patients received
everolimus for 14 days in combination with R - CHOP - 21.
François wondered if the synthetic compound would
make everolimus more effective.
It did, with the two - drug combination killing off pancreatic cancer cells more effectively than
everolimus alone.
In mice, the anti-angiogenic mTOR
inhibitor everolimus did not alter cognitive functions but led to weight loss and modification of cell metabolism in brain regions involved in sleep / wake cycle or food intake, likely connected to fatigue.
«Inhibiting mTOR signaling
using everolimus, a targeted therapy, known as a rapalog, for patients with lung and gastroenteropancreatic NETs, has been approved by the FDA.
While everolimus can extend some patients» lives by holding tumors in check, it does little to make them regress and is not effective for many people.
«This is important because we're focused
on everolimus, a drug that is already approved, non-toxic and given to patients.
The targeted
therapy everolimus may be safely combined with R - CHOP for new, untreated diffuse large B - cell lymphoma according to the results of a pilot study by Mayo Clinic researchers published in the Lancet Haematology.
And an earlier study of pulmonary fibrosis patients who
took everolimus found that among 11 patients who had lung transplants, there was no increased incidence of wound - healing / anastomosis problems.
about FDA
approves everolimus for tuberous sclerosis complex - associated partial - onset seizures
The phase III study was conducted among 366 patients with TSC and epilepsy from 25 countries who were randomly assigned to either a placebo, a low dose
of everolimus or a higher dose.
In an international study, the
drug everolimus has been shown to significantly reduce the frequency of seizures in patients with treatment - resistant epilepsy and tuberous sclerosis complex (TSC)-- a genetic disease that causes malformations and tumors in the brain and other vital organs.
Half of the patients were randomly assigned to receive angioplasty
with everolimus - eluting stent and half received bypass surgery.
This
makes everolimus, an mTOR inhibitor, a potential candidate to treat these mTOR - associated disorders, says Dr. Franz.
Taking that concept into biomedical research has yielded a breakthrough: This past May the mTOR
inhibitor everolimus was approved by the U.S. Food and Drug Administration for the treatment of advanced pNET, the first drug in this class approved for this disease.
In 2011, based on initial findings from two clinical trials, the Food and Drug Administration approved sunitinib and
everolimus for patients with pancreatic neuroendocrine tumors.
The number of severe adverse events and events leading to discontinuation of the study was consistent with findings of previous studies of
everolimus, according to Dr. Franz.
«The median percentage reduction in seizure frequency was more than 29 percent for patients on a low - dose regimen of
everolimus and nearly 40 percent for patients with high - dose regimen to the drug,» says David Franz, MD, founding director of the TSC Clinic at Cincinnati Children's Hospital Medical Center and the study's senior author.
Serious adverse events occurred in 3 percent of patients who received placebo and 14 percent of those who received a low - dose or high - dose of
everolimus.
The study, called the Bypass Surgery Versus Everolimus - Eluting Stent Implantation for Multivessel Coronary Artery Disease (BEST) trial, is one of only two randomized controlled trials to compare bypass to angioplasty since the introduction of
everolimus - eluting stents, a new generation of drug - eluting stent.
Next, researchers paired the compound with
everolimus.
Finding new treatments is critical because less than 5 percent of patients with pancreatic neuroendocrine tumors respond to
everolimus, the most commonly used pharmaceutical, François said.
That an existing drug can be made more effective is especially encouraging because the synthetic compound that was paired with
everolimus is already undergoing human clinical trials, Francois said.
Therefore, Mayo Clinic researchers decided to test a regimen that combined the standard R - CHOP with
everolimus.
«The encouraging outcome results and toxicity profile of this new regimen, along with the worldwide availability of
everolimus, make it potentially applicable to the large population of DLBCL patients.»
The everolimus, R - CHOP combination was well - tolerated by patients with no dose - limiting toxicity reached within the planned dose escalation.
Second, clinical studies have documented the single - agent efficacy of
everolimus (an mTOR inhibitor) in relapsed DLBCL.
«Because the study showed a statistically significant benefit among patients whose disease progressed on an aromatase inhibitor, a larger phase III study comparing this combination to other approved therapies used after initial therapies fail, like exemestane and
everolimus, should be done.»
One group had undergone bypass surgery, the other PCI with a new generation of stent that is coated with the drug
everolimus to inhibit inflammation and scar tissue growth.
Adding metformin to a combination of
everolimus plus letrozole for women with advanced or recurrent endometrioid endometrial cancer might offer clinical benefits.
This study is to evaluate use of
everolimus and tacrolimus in a prospective manner to see if the use of these two medications results in lower tumor recurrence and better patient survival than tacrolimus and mycophenolic acid / mycophenolate mofetil after liver transplantation for HCC.
Updated results from
the everolimus trial were published in September 2016.
The mTOR inhibitors (rapamycin,
everolimus) activate autophagy by blocking mTOR.