Enzalutamide adds five months survival in late-stage prostate cancer

August 16, 2012

Results of a phase III clinical trial of the drug Enzalutamide, published yesterday in the New England Journal of Medicine, show the drug extends life by an average five months in the most advanced stages of prostate cancer.

"This is a major advance. Not only do we see more than from traditional , but the side effects of Enzalutamide are much lower. It provides both more benefit and less harm – you get the quantification of more life, but also see quality of life improvements," says study co-author, Thomas Flaig, MD, medical director of the University of Colorado Cancer Center's Clinical Investigations Shared Resource and associate professor of medicine at the University of Colorado School of Medicine.

The study, known by the acronym AFFIRM, followed 1199 patients with that had progressed despite both hormonal and chemotherapy treatments, with 2/3 of patients receiving the drug Enzalutamide versus control. Median overall survival for patients in the treatment arm of the trial was 18.4 months compared to 13.6 months for patients in the placebo arm. In addition to prolonged survival, patients given Enzalutamide showed meaningful improvement in other measures including PSA blood levels, an increase from 3.0 months to 8.3 months in time until PSA progression, and an increase from 2.9 months to 8.3 months in overall progression-free survival.

The once-a-day oral drug works by blocking prostate cancer's ability to supply itself with androgens – hormones including testosterone that otherwise drive the cancer's growth. It does this by binding to cancer cells' – the waving tentacles on the outsides of cells that are designed to grab specific molecules as they float past. Enzalutamide plugs these receptors, removing their ability to grab androgen.

This out-competition for space in androgen receptors is not a new strategy. But when treated with existing anti-androgen drugs, prostate cancer tends to pull androgen receptors inside the cell walls, into a cell's nucleus where the receptors are shielded from drugs but can continue to trap androgens and thus signal growth. In addition to plugging receptors, Enzalutamide inhibits this nuclear translocation.

"Prostate cancer has traditionally been viewed as having two phases," Flaig says, "first is the hormone-sensitive stage and second is the stage at which the disease is no longer dependent on hormones and we're forced to turn to more toxic chemotherapies." Even a few years ago, the use of a hormonal agent in this second phase of prostate cancer would have been viewed at futile. Beyond establishing a new treatment for advanced prostate cancer, this study also helps to redefine "hormone-refractory" prostate cancer and proves that androgen-targeted treatments continue to be relevant later into the disease process than previously believed.

"This approach represents a much more potent and effective means of targeting the androgen receptor than possible with previously available agents. While this study examined the effect of adding Enzalutamide to standard androgen deprivation therapy, future studies could explore a single agent approach with this drug to treat prostate cancer," Flaig says. Another major study to look at this pre-chemotherapy activity is underway.

"We are in a renaissance period in the medical therapy of prostate cancer," Flaig says. "Enzalutamide is a key member of a half dozen new and emerging drugs and the challenge of the next five years is to discover how to best time and potentially combine these new agents. But even at this early stage, Enzalutamide is a game changer."

Explore further: New target, new drug in breast cancer

Related Stories

New target, new drug in breast cancer

June 4, 2012
Many breast cancers depend on hormones including estrogen or progesterone for their survival and proliferation. Eight years of lab work at the University of Colorado Cancer Center and elsewhere suggest that the androgen (AR) ...

New drugs, new ways to target androgens in prostate cancer therapy

June 20, 2012
Prostate cancer cells require androgens including testosterone to grow. A recent review in the British Journal of Urology International describes new classes of drugs that target androgens in novel ways, providing alternatives ...

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

August 15, 2012
The head of one of the UK's leading cancer research organisations has hailed a golden age in prostate cancer drug discovery as for the fourth time in two years results are published finding a new drug can significantly extend ...

Cabazitaxel with radiation and hormone therapy may improve prostate cancer survival

January 12, 2012
Jefferson's Kimmel Cancer Center has started a Phase I clinical trial investigating the latest prostate cancer chemotherapy drug to extend survival, Cabazitaxel, in combination with radiation and hormone therapy. This first-of-its-kind ...

Study identifies new prostate cancer drug target

February 6, 2012
Research led by Wanguo Liu, PhD, Associate Professor of Genetics at LSU Health Sciences Center New Orleans, has identified a new protein critical to the development and growth of prostate cancer. The findings are published ...

Recommended for you

Researchers discover a new target for 'triple-negative' breast cancer

November 20, 2017
So-called "triple-negative" breast cancer is a particularly aggressive and difficult-to-treat form. It accounts for only about 10 percent of breast cancer cases, but is responsible for about 25 percent of breast cancer fatalities.

Clinical trial suggests new cell therapy for relapsed leukemia patients

November 20, 2017
A significant proportion of children and young adults with treatment-resistant B-cell leukemia who participated in a small study achieved remission with the help of a new form of gene therapy, according to researchers at ...

Study reveals new mechanism used by cancer cells to disarm attacking immune cells

November 20, 2017
A new study by researchers at The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute (OSUCCC - James) identifies a substance released by pancreatic cancer cells that protects ...

Cell-weighing method could help doctors choose cancer drugs

November 20, 2017
Doctors have many drugs available to treat multiple myeloma, a type of blood cancer. However, there is no way to predict, by genetic markers or other means, how a patient will respond to a particular drug. This can lead to ...

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.