FDA Approves Erleada (apalutamide) for Non-Metastatic Castration-Resistant Prostate Cancer

The U.S. Food and Drug Administration, has approved Erleada (apalutamide) for the treatment of patients with prostate cancer that has not spread (non-metastatic), but that continues to grow despite treatment with hormone therapy (castration-resistant). This is the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer.

“The FDA evaluates a variety of methods that measure a drug’s effect, called endpoints, in the approval of oncology drugs. This approval is the first to use the endpoint of metastasis-free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “In the trial supporting approval, Erleada had a robust effect on this endpoint. This demonstrates the agency’s commitment to using novel endpoints to expedite important therapies to the American public."

According to the National Cancer Institute (NCI) at the National Institutes of Health, prostate cancer is the second most common form of cancer in men in the U.S.. The NCI estimates approximately 161,360 men were diagnosed with prostate cancer in 2017, and 26,730 were expected to die of the disease. Approximately 10 to 20 percent of prostate cancer cases are castration-resistant, and up to 16 percent of these patients show no evidence that the cancer has spread at the time of the castration-resistant diagnosis.

Erleada works by blocking the effect of androgens, a type of hormone, on the tumor. These androgens, such as testosterone, can promote tumor growth.

The safety and efficacy of Erleada was based on a randomized clinical trial of 1,207 patients with non-metastatic, castration-resistant prostate cancer. Patients in the trial either received Erleada or a placebo. All patients were also treated with hormone therapy, either with gonadotropin-releasing hormone (GnRH) analog therapy or with surgery to lower the amount of testosterone in their body (surgical castration). The median metastasis-free survival for patients taking Erleada was 40.5 months compared to 16.2 months for patients taking a placebo.

Common side effects of Erleada include fatigue, high blood pressure (hypertension), rash, diarrhea, nausea, weight loss, joint pain (arthralgia), falls, hot flush, decreased appetite, fractures and swelling in the limbs (peripheral edema).

Severe side effects of Erleada include falls, fractures and seizures.

This application was granted Priority Review, under which the FDA’s goal is to take action on an application within 6 months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

The sponsor for Erleada is the first participant in the FDA’s recently-announced Clinical Data Summary Pilot Program, an effort to provide stakeholders with more usable information on the clinical evidence supporting drug product approvals and more transparency into the FDA’s decision-making process. Soon after approval, certain information from the clinical summary report will post with the Erleada entry on Drugs@FDA and on the new pilot program landing page.

FDA Approves Erleada (apalutamide) for Non-Metastatic Castration-Resistant Prostate Cancer

FDA approves non-alcoholic Docetaxel Injection

In continuation of my update on Docetaxel

Teikoku Pharma USA, Inc. ("Teikoku" or "the Company") announced today that the U.S. Food and Drug Administration ("FDA") has approved Docetaxel Injection, Non-Alcohol Formula ("Docetaxel Injection") for the treatment of breast cancer, non-small cell lung cancer, prostate cancer, gastric adenocarcinoma, and head and neck cancer. Teikoku entered into an exclusive licensing agreement with Eagle Pharmaceuticals Inc. ("Eagle Pharmaceuticals") in October 2015 to market, sell and distribute Docetaxel Injection in the U.S.

The main difference, compared to other docetaxel formulations, is that Docetaxel Injection is the first non-alcohol formulation approved in the U.S. Further differentiating it from some of the currently marketed docetaxel formulations is that Teikoku's Docetaxel Injection:

• Requires no prior dilution with a diluent and is ready to add to the infusion solution; and
• Is available in three presentations: 20mg/ml in single-dose vials, and 80 mg/4 mL or 160 mg/8 mL in multiple-dose vials.............

FDA approves non-alcoholic Docetaxel Injection

Scientists develop powerful new animal model for metastatic prostate cancer

Prostate cancer is the most common form of cancer in men. Affecting about 1 in 6 men, it is the second deadliest cancer. Research has been stymied by imperfect animal models of the disease, which are costly, take considerable time to develop, and fail to mimic the most lethal aspects of the illness. Now, Cold Spring Harbor Laboratory (CSHL) scientists have developed a new method to rapidly create much better mouse models for metastatic prostate cancer. This discovery allows scientists to investigate the causes of the disease while at the same time testing new therapeutics to treat it.

More at 

Ref: http://cancerdiscovery.aacrjournals.org/content/early/2014/01/24/2159-8290.CD-13-0346

Scientists develop powerful new animal model for metastatic prostate cancer  

Soy and tomato may be effective in preventing prostate cancer

Tomatoes and soy foods may be more effective in preventing prostate cancer when they are eaten together than when either is eaten alone, said a University of Illinois study.

"Eating tomato, soy, and the combination all significantly reduced prostate cancer incidence. But the combination gave us the best results. Only 45 percent of mice fed both foods developed the disease compared to 61 percent in the tomato group, and 66 percent in the soy group," he said.

Prostate cancer is the most frequently diagnosed cancer in men, but the disease has nearly a 100 percent survival rate if it's caught early. In older men, it is often a slow-growing cancer, and these men often choose watchful waiting over radiation and surgical treatments that have unwelcome side effects, said Krystle Zuniga, co-author of the paper.

Soy isoflavone serum and prostate levels in the mice are similar to those found in Asian men who consume one to two servings of soy daily. In countries where soy is eaten regularly, prostate cancer occurs at significantly lower levels, Erdman noted.

How much soy and tomato should a 55-year-old man concerned about prostate health eat in order to receive these benefits?

"The results of the mouse study suggest that three to four servings of tomato products per week and one to two servings of soy foods daily could protect against prostate cancer," Zuniga said.

According to the scientists, these findings reinforce the recommendation that we should all eat a wide variety of whole fruits and vegetables.

"It's better to eat a whole tomato than to take a lycopene supplement. It's better to drink soy milk than to take soy isoflavones. When you eat whole foods, you expose yourself to the entire array of cancer-fighting, bioactive components in these foods," Erdman said.

The researcher's whole-food recommendation is bolstered by the way soy germ performed in this study. He noted that soy germ has a very different isoflavone profile than the rest of the soybean.

"Of the isoflavones, genistein gets most of the attention. But soy germ is very high in the other isoflavones, daidzein and glycitein, and low in genistein," he said...

Ref : http://cancerpreventionresearch.aacrjournals.org/content/early/2013/04/16/1940-6207.CAPR-12-0443

Soy and tomato may be effective in preventing prostate cancer

Abiraterone improves outcomes for prostate cancer prior to chemo

In continuation of my update on abiraterone

Abiraterone improves outcomes for prostate cancer prior to chemo

GenSpera plans to initiate G-202 Phase II trial in prostate cancer

 We know that, a Mediterranean plant (see pic), Thapsia garganica, a simple weed, is the original source of G202. For millennia, the plant has been known to be poisonous to animals; in the days of desert caravans, it was called the “death carrot” for the unfortunate fate awaiting any camel that ingested it. Researchers at the Johns Hopkins Kimmel Cancer Center in the US and their Danish collaborators hoped to harness the toxicity of the plant in a controlled way that could be used to treat cancer in people.

They did so by taking apart the toxic compound, thapsigargin, produced by the plant and altering its chemical structure. The resulting prodrug, G202, is not active until it comes into contact with a particular protein produced by certain tumors. This prostate-specific membrane antigen (PMSA) is released by cells lining the outside of prostate and other tumors. Samuel Denmeade, the study’s lead author, uses the image of a hand grenade. The presence of PMSA essentially “pulls the pin” of the G202 grenade. In its active form, the drug is able to kill not only the tumor, but the blood vessels that provide it with nutrients.

A recent study of  G202,  looked at the effects of the drug on human prostate tumors grown in mice, and compared it to docetaxel, a chemotherapy drug already in use. G202 clearly came out on top, reducing by half the size of seven out of nine tumors; docetaxel achieved the same effect on only one out of eight tumors. Similar results for G202 were also seen in experiments with human breast, kidney and bladder cancer.

These promising results encouraged doctors to test the safety of G202 in a phase I clinical trial, involving 29 cancer patients at advanced stages of the disease.  

Now its  good news that,......

GenSpera plans to initiate G-202 Phase II trial in prostate cancer

Golden age of prostate cancer treatment hailed as fourth drug in two years extends life

We know that, Enzalutamide (formerly known as MDV3100, see the structure) is an experimental androgen receptor antagonist drug developed by the pharmaceutical company Medication for the treatment of castration-resistant prostate cancer currently in phase 3 clinical trials. Results so far have been encouraging; Medivation has reported up to an 89% decrease in prostate specific antigen serum levels after a month of taking the medicine. Early preclinical studies also suggest that enzalutamide inhibits breast cancer cell growth. 

Researchers from Institute of Cancer Research, London, and its partner hospital The Royal Marsden NHS Foundation Trust jointly led the new Phase III trial of enzalutamide and the Phase III trials of two other drugs, cabazitaxel and abiraterone. Abiraterone was also discovered at The Institute of Cancer Research and was recently made available on the NHS. A further drug sipuleucel-T has also been shown to extend life in the two-year period.

"What we're seeing now is an unprecedented period of success for prostate cancer research, with four new drugs shown to extend life in major clinical trials in just two years, and several others showing promise. It truly is a golden age for prostate cancer drug discovery and development" claims Prof. Martin Gore....

Golden age of prostate cancer treatment hailed as fourth drug in two years extends life

GEN | News Highlights:Green Tea and Gold Nanoparticles Destroy Prostate Tumors

In continuation of my update on green tea

Scientists report on the development of a radioactive gold nanoparticle for prostate cancer therapy that they claim is far less toxic to normal tissues than traditional radiation therapy and results in massive reduction in tumor volume and increased survival in experimental mice after just one dose. The nanoparticles, derived from the Au-198 isotope, incorporate an extract from green tea known as epigallocatechin-gallate (EGCg), which effectively latches the nanoparticles onto the prostate tumor cells and facilitates their internalization.

GEN | News Highlights:Green Tea and Gold Nanoparticles Destroy Prostate Tumors

For advanced prostate cancer, new drug slows disease

In continuation of my update on abiraterone

The study is the first randomized clinical trial to document expanded benefits among a particular group of prostate cancer patients in whom the disease had spread. The medication, abiraterone acetate -- marketed as Zytiga -- also delayed the development of pain and deterioration of the patients' overall condition.

The researchers say the medication could provide new treatment options.

"This drug extended lives and gave patients more time when they weren't experiencing significant pain from the disease,'' said the principal.....

For advanced prostate cancer, new drug slows disease

Advanced Prostate Cancer Drug May Help at Earlier Stage

In continuation of my update on abiraterone

Advanced Prostate Cancer Drug May Help at Earlier Stage:  A drug approved to treat advanced prostate cancer appears to help men who have localized high-risk prostate cancer if given before surgery. Adding Zytiga (abiraterone) to conventional hormonal treatments eliminated or nearly...

Abiraterone acetate can help eliminate prostate tumors

In continuation of my update Abiraterone

Abiraterone acetate can help eliminate prostate tumors: A hormone-depleting drug approved last year for the treatment of metastatic prostate cancer can help eliminate or nearly eliminate tumors in many patients with aggressive cancers that have yet to spread beyond the prostate, according to a clinical study to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO), June 1-5, in Chicago.

In continuation of my update on curcumin,,,,

Curcumin, an active component of the Indian curry spice turmeric, may help slow down tumor growth in castration-resistant prostate cancer patients on androgen deprivation therapy (ADT), a study from researchers at Jefferson's Kimmel Cancer Center suggests. More

 Curry spice component may help slow prostate tumor growth

Drug May Slow Early Prostate Cancer: Study

In continuation of my update on Dutasteride (Avodaart)

New research suggests that Avodart, a drug used to treat an enlarged prostate gland, may help slow the progression of early stage prostate cancer, reducing the need for aggressive treatment in some men. 

Avodart belongs to a class of drugs called 5-alpha reductase inhibitors. These drugs work by interfering with the effects of certain male hormones on the prostate. In the three-year study, prostate cancer progressed in 38 percent of 144 men with early prostate cancer who were treated with Avodart and 48 percent of the 145 men who received a placebo....

More...

FDA approves new targeted therapy to treat men with advanced prostate cancer..

In continuation of my update on  Abiraterone ....

We know that, Abiraterone (tradename Zytiga) is a drug currently under investigation for use in castration-resistant prostate cancer (formerly hormone-resistant or hormone-refractory prostate cancer) (prostate cancer not responding to androgen deprivation or treatment with antiandrogens). 

It blocks the formation of testosterone by inhibiting CYP17A1 (CYP450c17), an enzyme also known as 17α-hydroxylase/17,20 lyase. This enzyme is involved in the formation of DHEA and androstenedione, which may ultimately be metabolized into testosterone.This drug was initially discovered at the Institute of Cancer Research in London. 

Recently  approved abiraterone. It improves, by nearly four months, the overall survival rate of men with metastatic chemotherapy- and castration-resistant prostate cancer. Since 2005, the Prostate Cancer Foundation invested $8.2 million in over six research projects to advance independent academic research for investigating abiraterone's mechanism of action and biomarkers to predict patient response...

More....

Researchers identify drug candidate that can treat prostate cancer

Drug candidate, developed from a naturally occurring anti-cancer agent found in cruciferous vegetables such as cabbages and broccoli, for prostate cancer...
Researchers identify drug candidate that can treat prostate cancer

ProstaCaid (33-ingredient comprehensive polyherbal preparation) against prostate cancer......

We have seen  many benefits of natural products rich in  Quercetin,   Epigallocatechin gallate (EGCG) and many other polyphenol antioxidant from natural products like green tea, broccoli peaches and plums. Interestingly, now researchers from  Columbia University have come up with an interesting finding, i.e., ProstaCaid is a 33-ingredient comprehensive polyherbal preparation with supplements of vitamin C, vitamin D3, zinc, selenium, quercitin, 3,3′-diinodolymethane (DIM), and lycopene was able to stop abnormal cell growth and induce apoptosis (programmed cell death) in both hormone sensitive and hormone resistant prostate cancer cell lines at unusually low concentrations, which makes the findings more significant...

Herbal extracts include the extracts from turmeric root, saw palmetto berry, grape skin, pomegranate, pumpkin seed, pygeum bark, sarsaparilla root, green tea, and Japanese knotweed. Hence, it is rich in natural polyphenols, including quercetin, resveratrol, epigallocatechin gallate (EGCG), and ellagic acid, which have previously demonstrated anticancer potential. The unique formula contains 3 medicinal mushrooms grown on an herbal-enhanced medium. The mushrooms included are Phellinus linteus, Ganoderma lucidum, and Coriolus versicolor, each with known anticancer properties.

Researchers claim that, ProstaCaid was designed based on constituents that exhibit antiprolifetaive, antioxidant, and apoptotic activities; however, its efficacy and the mechanisms of action are yet to be examined. Researchers looked at the effectiveness of the preparation in suppressing several types of prostate cancer cell lines in culture and attempt to delineate the mechanism of action for justification in pursuing animal to determine efficicacy invivo.

Researchers conclude that, the anticancer activity of ProstaCaid may be ascribed to its polyphenolic flavonoids and curcuminoids derived from various herbs as well as other supplements, such as DIM. The preparation contains supplements such as quercetin (15%), Curcuma longa root extract complex with enhanced bioavailability (BCM-95; 20%), DIM (3%), and resveratrol (0.2%). Some of these components have shown a strong doseand time-dependent growth inhibition and apoptotic death in prostate cancer cells; 25 mM of quercetin inhibited about 50% PC3 cell growth for 72 hours. At 24 hours, 50 mM and 100 mM quercetin induced G2/M arrest and apoptosis, manifested by the decrease in G2/M-related protiens.

Researchers summarise  that,    ProstaCaid has anti-cancer activities in both AD and AI prostate cancer cells at very low concentrations (25 mg/mL). It also suggests that ProstaCaid inhibits cell growth and survival, at least through the inhibition of AKT and MAPK signaling. The effect on AI cell lines is especially of importance as there is presently no curative therapy for hormone refractory prostate cancer.

Researchers postulate that ProstaCaid may affect activity of Cdc2/cyclin B1 kinase by reducing this complex formation. Cdc2 could be dephosphorylated by Cdc25C and become inactive or be phosphorylated by protein kinase, such as Wee1, and then converted into an inactive form. They also suggest that more studies are needed in the future to test it and to define its upstream events in PC3 cells.

Ref : Jun Yan and Aaron E. Katz, Integr Cancer Ther 2010 9: 186

FDA approves Jevtana to treat men with prostate cancer

In continuation of my update on Cabazitaxel......

FDA approves Jevtana to treat men with prostate cancer