Combination of contraceptive and cholesterol-lowering drugs kills cancer cells in a new way

The combination of a cholesterol-lowering drug, Bezafibrate (first left structure), and a contraceptive steroid, Medroxyprogesterone Acetate (second right), could be an effective, non-toxic treatment for a range of cancers, researchers at the University of Birmingham have found.

   

The findings published in the journal Cancer Research show that the drugs kill cancer cells in a completely new way.

Early stage clinical trials of the drugs in elderly patients with acute myeloid leukaemia (AML) have shown promising results, with survival three months longer on average than standard palliative care. The combination, known as BaP, has also been used alongside chemotherapy to successfully treat children with Burkitt's lymphoma (BL), the most common childhood cancer in Eastern Africa.

Until now it was uncertain whether the activity of the drugs against these two very different blood cancers was mediated by a common mechanism or by different effects in each cancer type.

The scientists, who were funded by Leukaemia & Lymphoma Research, used state of the art technology to interrogate the drug's effects on the metabolism and chemical make-up of AML and BL cells and found that in both cell types the drugs block an enzyme crucial to the production of fatty acids, which cancer cells need to grow and multiply. They also demonstrated that the ability of BaP treatment to deactivate this enzyme, called stearoyl CoA desaturase, was what prompted cancer cells to die.

Read More at Cancer Research

Combination of contraceptive and cholesterol-lowering drugs kills cancer cells in a new way

Combination therapy provides promising results in patients with advanced non-small cell lung cancer

An early phase study testing an anti-PDL1 agent in combination with standard chemotherapy in the treatment of advanced non-small cell lung cancer has provided promising early results, prompting multiple phase III studies in lung cancer. The findings are being presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

In this phase 1b study, patients with untreated non-small cell lung cancer received one of three standard platinum-based chemotherapy regimens (paclitaxel/carboplatin, pemetrexed/carboplatin or nab-paclitaxel/carboplatin) with MPDL3280A, an antibody targeting PD-L1. Early results from the 

Paclitaxel Carboplatin Pemetrexed

first 37 patients showed impressive response rates between 60-75 percent, comparing favorably to historical outcomes with chemotherapy alone, where historical response rates from randomized trials are around 30 - 35 percent. In addition, two complete responses already have been documented, with no evidence of lung cancer on CT scans.

"A complete response is not typically seen in patients with stage IV lung cancer," says the abstract's lead author, Stephen V. Liu, MD, assistant professor of medicine at Georgetown Lombardi Comprehensive Cancer Center. "And the response rates seen with MPDL3280A and chemotherapy were higher than one would expect with chemotherapy alone."

Combination therapy provides promising results in patients with advanced non-small cell lung cancer

STA, Helsinn announce approval of AKYNZEO for prevention of chemotherapy-induced CINV

In continuation of my update on AKYNZEO®

Australian biopharmaceutical company Specialised Therapeutics Australia (STA) and Helsinn, a Swiss group focused on building quality cancer care, announce that the Therapeutic Goods Administration (TGA) has approved AKYNZEO® for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy.

AKYNZEO® is the first approved fixed dose combination oral agent that targets two critical signalling pathways associated with CINV by combining netupitant, an NK1receptor antagonist, and palonosetron, a 5-HT3 receptor antagonist, in a single capsule for the prevention of CINV. 

"Cancer patients are burdened with having to take multiple drugs, often several times per day and certainly multiple times per cycle of chemotherapy, to reduce unwanted side effects. With every increased drug/schedule there is an increased risk of mistakes and/or non-compliance," said Professor Dorothy Keefe, Clinical Ambassador, Transforming Health and Professor of Cancer Medicine, University of Adelaide. "The availability of this combination of drugs, in a single capsule, allows 'once per cycle' dosing (which is even better than once per day dosing) for the benefit of the patient."

The approval of AKYNZEO® was based on the submission of Phase 2 and Phase 3 trials with AKYNZEO® in patients undergoing treatment with moderately and highly emetogenic chemotherapy regimens for a variety of tumour types. The most common adverse reactions reported by ≥ 1% of patients treated with AKYNZEO® for one or more cycles were headache, constipation and fatigue.

STA Chief Executive Officer Mr Carlo Montagner said AKYNZEO® was a valuable addition to STA's Oncology Supportive Care portfolio, providing patients with access to an effective and convenient antiemetic therapy. "We look forward to making this drug available to cancer patients around the country, for improved management of some of the most common side effects of chemotherapy, which can severely diminish a patient's quality of life. STA will now seek to have AKYNZEO® listed on the Pharmaceutical Benefits Scheme for reimbursement."

STA, Helsinn announce approval of AKYNZEO for prevention of chemotherapy-induced CINV

Risk for endophthalmitis no higher with Avastin, finds study

 In continuation of my update on Avastin



 Risk for endophthalmitis no higher with Avastin, finds study

Cholesterol-lowering statin drugs could delay prostate cancer growth in patients receiving ADT

In a study published online today by JAMA Oncology, the researchers report that men who had been taking statins since the start of androgen deprivation therapy (ADT) went a median of 27.5 months before their disease began to worsen, compared to 17.4 months for men who didn't take statins. The trial involved 926 patients, 70 percent of whom had their disease progress during a six-year period.

"This median 10-month benefit in delaying disease progression suggests that statins could be a valuable addition to our current therapies for prostate cancer," says the study's first author, Lauren Harshman, MD, medical oncologist at the Lank Center for Genitourinary Oncology at Dana-Farber. "These results are supported by multiple prior epidemiologic studies demonstrating that statin use may be associated with improved outcomes in prostate cancer, but require validation."

The trial grew out of laboratory studies that suggested statins could delay prostate cancer growth in patients receiving ADT. (ADT reduces the amount of androgen in the body, preventing prostate cancer cells from using it to fuel their growth. For many years, it has been the frontline treatment for patients with hormone-sensitive prostate cancer that has spread beyond the prostate gland.)

The laboratory phase of the research focused on a protein called SLCO2B1, which helps a variety of drugs and hormones enter cells. One of these immigrants to the cell is dehydro-epiandrosterone  sulfate (DHEAS), a precursor of testosterone, the hormone that spurs prostate cancer cell growth. Statin drugs, too, rely on SLCO2B1 to gain entry to cells.

More : http://oncology.jamanetwork.com/article.aspx?articleid=2288665

Cholesterol-lowering statin drugs could delay prostate cancer growth in patients receiving ADT

Dexamethasone May Help Prevent Severe Kidney Injury Following Heart Surgery

In continuation of my update on dexamethasone....

The anti-inflammatory drug dexamethasone helps prevent serious kidney complications that can arise following heart surgery, according to the results of a randomized clinical trial. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), could lead to a change in care for patients during cardiac operations.

Acute kidney injury (AKI) is one of the most devastating complications following cardiac surgery. Approximately 1% of patients undergoing cardiac surgery require dialysis to treat severe AKI that arises after surgery, and the incidence is higher among patients with pre-operative chronic kidney disease. These patients experience strikingly high death rates while in the hospital that exceed 40%. "One percent sounds like a small percentage, however given the fact that each year, over half a million people undergo heart surgery in the United States alone, this means that an estimated 5000 patients develop renal failure and of those about 2500 die as a result of this complication," said Kirolos Jacob, MD (University Medical Center, Utrecht, The Netherlands). He noted that these figures are rising due to the aging population.

Because heart surgery initiates an inflammatory reaction in the body that can have negative effects on the kidneys, Dr. Jacob and his colleagues wondered whether giving patients dexamethasone, an anti-inflammatory drug, could decrease the risk of severe AKI following cardiac surgery. The team analyzed the results of a large randomized controlled trial called the Dutch Dexamethasone for Cardiac Surgery (DECS) trial, which included 4465 patients undergoing cardiac surgery who were randomized to receive placebo or dexamethasone during surgery. The original trial tested whether dexamethasone could reduce the risk of a variety of major postoperative complications. In this analysis, the investigators specifically examined kidney failure and focused on the most severe form: AKI requiring dialysis.

Dexamethasone appeared to protect against the development of severe AKI. Patients who received the drug had about a 2.5-times lower risk of developing AKI requiring dialysis compared with those receiving a placebo.

"The beneficial effects of dexamethasone were particularly present in those who already had pre-existing kidney disease before heart surgery," said Dr. Jacob. "This reinforces the fact that this drug could be of major importance for the increasing elderly population with pre-existing kidney disease undergoing a heart operation."

Read more at : http://dx.doi.org/10.1681/ASN.2014080840

Dexamethasone May Help Prevent Severe Kidney Injury Following Heart Surgery 

Potential new painkiller provides longer lasting effects ..........

Medications have long been used to treat pain caused by injury or chronic conditions. Unfortunately, most are short-term fixes or cause side effects that limit their use. Researchers at the University of Missouri have discovered a new compound that offers longer lasting painkilling effects, and shows promise as an alternative to current anesthetics.

"Because of its versatility and effectiveness at quickly numbing pain in targeted areas, lidocaine has been the gold standard in local anesthetics for more than 50 years," said George Kracke, Ph.D., associate professor of anesthesiology and perioperative medicine at the MU School of Medicine and lead author of the study. "While lidocaine is effective as a short-term painkiller, its effects wear off quickly. We developed a new compound that can quickly provide longer lasting relief. This type of painkiller could be beneficial in treating sports injuries or in joint replacement procedures."

Painkillers work by interfering with the nervous system's transmission of nerve signals that the body perceives as pain. Lidocaine is used as an injectable pain reliever in minor surgical or dental procedures, or as a topical ointment or spray to relieve itching, burning and pain from shingles, sunburns, jellyfish stings and insect bites. The new compound developed at MU, boronicaine, could potentially serve many of those same functions as an injectable or topical painkiller.

National Academy of Sciences member M. Frederick Hawthorne, Ph.D., director of MU's International Institute of Nano and Molecular Medicine and a pioneer in the field of boron chemistry, synthesized boronicaine as a derivative of lidocaine. By changing aspects of the chemical structure of lidocaine, the researchers found that the new compound provided pain relief that lasted five times longer than lidocaine. In pre-clinical, early stage studies, boronicaine provided about 25 minutes of relief, compared to about five minutes of pain relief with lidocaine.

"Although some conditions may warrant the use of a short-lasting painkiller, in many cases a longer lasting anesthetic is a better option," Kracke said. "Having a longer lasting anesthetic reduces the dosage or number of doses needed, limiting the potential for adverse side effects." While other types of painkillers can provide longer pain relief than lidocaine, they can cause heart toxicity, gastrointestinal issues and other side effects. Preliminary findings show no toxicity in single-dose studies of boronicaine, though more studies are needed.

"Boronicaine could have distinct advantages over existing painkilling medications," said Hawthorne, who also serves as the Curators' Distinguished Professor of Chemistry and Radiology at MU. "We're conducting more research into the side effects of the compound, but in time it could very well become a useful material to use as an anesthetic."

Ref : http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201402369/pdf

Potential new painkiller provides longer lasting effects  

Viagra to prevent transmission of the malaria parasite?

By increasing the stiffness of erythrocytes infected by the causal agent of malaria, Viagra favors their elimination from the blood circulation and may therefore reduce transmission of the parasite from humans to mosquitoes. This astonishing discovery, made by scientists from the CNRS, INSERM, Université Paris Descartes -- at the Institut Cochin -- and the Institut Pasteur, working in collaboration with a team from the London School of Hygiene and Tropical Medicine, could lead to a treatment to reduce the spread of malaria within a population. Their work is published in PLOS Pathogens on 7 May 2015.

More : http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004815



Viagra to prevent transmission of the malaria parasite? 

Plant-derived compound targets cancer stem cells

In continuation of my updates on cauliflower, cabbage, broccoli

A compound and an enzyme that occur naturally in cruciferous vegetables--cauliflower, cabbage, broccoli and Brussels sprouts--may help prevent recurrence and spread of some cancers, according to researchers. When they treated human cervical cancer stem cells with phenethyl isothiocyanate (PEITC) in a Petri dish, about 75 percent died within 24 hours using a 20-micromolar concentration of the compound.  

A compound and an enzyme that occur naturally in cruciferous vegetables -- cauliflower, cabbage, broccoli and Brussels sprouts -- may help prevent recurrence and spread of some cancers, according to associate professor Moul Dey of the South Dakota State University Department of Health and Nutritional Sciences. She has been doing research on phenethyl isothiocyanate (PEITC) through a five-year grant from the National Institutes of Health for more than $875,000 and support from the South Dakota Agricultural Experiment Station.

The precursor compound and enzyme in cruciferous vegetables combine during the chewing process to produce PEITC within the body, Dey explained. Though PEITC is a good candidate to develop as a dietary supplement, studies have also shown that sufficient cancer-preventing levels of PEITC can be achieved through diet alone.

Role of cancer stem cells

When cancer is treated with chemotherapy or radiation, the tumor disappears but the cancer stem cells live on. "These cells are frequently resistant to conventional therapies," Dey said.

Though cancer stem cells make up less than 5 percent of a tumor, they can regenerate the original tumor and migrate through the blood vessels spreading cancer to secondary locations.

"These tiny cells are very difficult to detect in a tumor," Dey pointed, adding that for a long time scientists did not even know they existed. "It's like finding a needle in a haystack."

Promising Results

When Dey and her team treated human cervical cancer stem cells with PEITC in a Petri dish, about 75 percent died within 24 hours using a 20-micromolar concentration of the compound.

In other experiments, Dey and her team have found that lower concentrations of PEITC are still very effective. Working with SDSU veterinary pathologist David Knudsen, Dey and her team found that 10-micromolar concentrations of PEITC can dramatically prevent the spread of cancer in mouse lung tissue.

"Preliminary evidence has shown a quite dramatic difference between the lung sections from the PEITC-treated and untreated mice," Dey said. However, she cautioned, although mice provide a model for human diseases, further testing is necessary to determine whether outcomes will be similar in humans.

Based on information from scientific literature, the concentrations of PEITC that Dey and her team typically use in their research -- 5 to 15 micromolars -- may be achieved through diets rich in certain types of cruciferous vegetables, particularly land and watercress.

Next, she and her team will examine how PEITC is able to overcome the resistance mechanisms that protect these stem cells from other drugs. "That's the second piece of this work," Dey added.

Plant-derived compound targets cancer stem cells 

FDA Expands Uses of Vyvanse to Treat Binge-Eating Disorder

Lisdexamfetamine (contracted from L-lysine-dextroamphetamine) is a central nervous system (CNS) stimulant prodrug of thephenethylamine and amphetamine chemical classes. Its chemical structure consists of dextroamphetamine coupled with the essential amino acid L-lysine. Lisdexamfetamine itself is inactive and acts as a prodrug to dextroamphetamine upon cleavage of the lysine portion of the molecule.

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The U.S. Food and Drug Administration today expanded the approved uses of Vyvanse (lisdexamfetamine dimesylate) to treat binge-eating disorder in adults. The drug is the first FDA-approved medication to treat this condition.

In binge-eating disorder, patients have recurrent episodes of compulsive overeating during which they consume larger amounts of food than normal and experience the sense that they lack control. Patients with this condition eat when they are not hungry and often eat to the point of being uncomfortably full. Patients may feel ashamed and embarrassed by how much they are eating, which can result in social isolation. Binge-eating disorder may lead to weight gain and to health problems related to obesity.

FDA Expands Uses of Vyvanse to Treat Binge-Eating Disorder

FDA Approves Prezcobix (darunavir and cobicistat) for HIV-1 Infection in Adults

In continuation of my update on darunavir  

Janssen Therapeutics, Division   of    Janssen    Products, LP     (Janssen), today announced the U.S. Food and Drug Administration (FDA)    has approved Prezcobix   (darunavir 800 mg/cobicistat 150 mg) tablets, an HIV-1  protease inhibitor combined with a CYP3A4 inhibitor, for the treatment of human immunodeficiency virus (HIV-1) in combination with other antiretroviral agents for treatment-naive and treatment-experienced adults with no darunavir resistance-associated substitutions.

FDA Approves Prezcobix (darunavir and cobicistat) for HIV-1 Infection in Adults

FDA Approves Glyxambi (empagliflozin and linagliptin) for Type 2 Diabetes

In continuation of my update on empagliflozin

The U.S. Food and Drug Administration (FDA) has approved Glyxambi (empagliflozin/linagliptin) tablets, from Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Eli Lilly and Company (NYSE: LLY), as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) when both empagliflozin and linagliptin are appropriate treatments. Glyxambi is not recommended in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Glyxambi has not been studied in patients with a history of pancreatitis, and it is unknown if using Glyxambi increases the risk of developing pancreatitis in these patients.

Glyxambi is not recommended in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Glyxambi has not been studied in patients with a history of pancreatitis, and it is unknown if using Glyxambi increases the risk of developing pancreatitis in these patients.

FDA Approves Glyxambi (empagliflozin and linagliptin) for Type 2 Diabetes

FDA Approves Ibrance (palbociclib) for Postmenopausal Women with Advanced Breast Cancer

In continuation of my update on palbociclib

The U.S. Food and Drug Administration today granted accelerated approval to Ibrance (palbociclib) to treat advanced (metastatic) breast cancer.

Breast cancer in women is the second most common type of cancer in the United States. It forms in the breast tissue and in advanced cases, spreads to surrounding normal tissue. The National Cancer Institute estimates that 232,670 American women were diagnosed with breast cancer and 40,000 died from the disease in 2014.

Ibrance works by inhibiting molecules, known as cyclin-dependent kinases (CDKs) 4 and 6, involved in promoting the growth of cancer cells. Ibrance is intended for postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have not yet received an endocrine-based therapy. It is to be used in combination with letrozole, another FDA-approved product used to treat certain kinds of breast cancer in postmenopausal women.

FDA Approves Ibrance (palbociclib) for Postmenopausal Women with Advanced Breast Cancer

FDA Approves Dutrebis (lamivudine and raltegravir) for HIV-1 Infection

   

The United States Food and Drug Administration (FDA) has approved Dutrebis, a fixed dose combination tablet containing 150 mg of lamivudine and 300 mg of raltegravir. Dutrebis tablet is approved for use in combination with other antiretroviral products for the treatment of HIV-1 infection in adults and pediatric patients greater than or equal to 6 years of age weighing at least 30 kg. The recommended dosage of Dutrebis is one tablet taken twice daily with or without food.

Dutrebis approval was based on an open-label, single dose, randomized, two-period, crossover study in healthy subjects (n=108). One Dutrebis fixed dose combination table was shown to provide comparable lamivudine and raltegravir exposures to one Epivir 150 mg tablet plus on Isentress 400 mg tablet. Due to the higher bioavailability of raltegravir contained in Dutrebis, the exposures provided by the 300 mg dose of raltegravir are comparable to 400 mg of ralegravir given as the raltegravir poloxamer formulation (Isentress), which accounts for the difference in raltegravir dose.

FDA Approves Dutrebis (lamivudine and raltegravir) for HIV-1 Infection

FDA Approves Lenvima (lenvatinib) for Differentiated Thyroid Cancer

LENVIMA, a kinase inhibitor, is the mesylate salt of lenvatinib. Its chemical name is 4- [3chloro-4-(N’-cyclopropylureido)phenoxy]-7-methoxyquinoline-6-carbox- amide methanesulfonate. The molecular formula is C₂₁H₁₉ClN₄O₄•CH₄O₃S, and the molecular weight of the mesylate salt is 522.96. The chemical structure of lenvatinib mesylate is:

The U.S. Food and Drug Administration today granted approval to Lenvima(lenvatinib) to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease progressed despite receiving radioactive iodine therapy (radioactive iodine refractory disease).

FDA Approves Lenvima (lenvatinib) for Differentiated Thyroid Cancer