New targeted therapy for advanced prostate cancer shows anti-tumor activity in clinical trials
Few available treatment options exist once prostate cancer has spread to other parts of the body and has failed to respond to therapies that involve blocking the male hormone androgen. Patients with advanced, hormone-refractory prostate cancer usually die from the disease after 12 to 18 months, so new therapies are desperately needed.
At the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, today (Thursday), researchers will report that a new drug that specifically targets a protein found on the surface of prostate cancer cells has performed well in a phase I clinical trial, and a phase II trial has started. The drug reduced levels of circulating tumour cells (CTC) and levels of prostate specific antigen (PSA), a marker for tumour activity, in patients who had already failed previous chemotherapy and hormone treatments.
The drug is made up of a monoclonal antibody, which targets a protein called prostate specific membrane antigen (PSMA), linked to a cancer cell-killing drug called monomethyl auristatin E (MMAE), which disrupts tubulins – the tiny molecules inside a cell that are essential for cell division. The PSMA antibody drug conjugate (PSMA ADC) binds to the PSMA on the surface of the prostate cancer cell and is absorbed into the cell where the MMAE is released, causing cell cycle arrest and cell death.
Professor Daniel Petrylak, who was Professor of Medicine at Columbia University Medical Center (USA) when the phase I trial started and who is now Director of the Prostate Cancer Program/Genitourinary Cancer Program and co-director of the Signal Transduction Program at Yale University Medical Centre (USA), said: "By conjugating the antibody with a chemotherapeutic agent, we hoped that this would lead to more targeted therapy, which would have fewer toxic side-effects and would be more effective against the cancer."
Prof Petrylak and his colleagues from other US cancer centres recruited 50 patients to the phase I clinical trial. The patients had the most advanced form of prostate cancer, which had spread to the bone and other organs; they had failed hormone therapy and had received up to two previous chemotherapies. The researchers treated them with doses of PSMA ADC at levels ranging from 0.4 to 2.8 mg/kg, by intravenous infusion, over a period of three weeks per cycle, and for up to four treatment cycles.
The researchers detected anti-tumour activity among the patients who were treated at the higher doses. About half of the patients who received doses of 1.8 mg/kg or more showed either a 50% or more reduction in PSA levels, or a fall in CTC in the blood to less than five cells per 7.5 ml of blood, or both.
The drug was generally well tolerated by patients, although levels of white blood cells were significantly reduced (neutropenia) at the highest dose of 2.8 mg/kg and one patient died. The researchers say the cause of the death is unclear.
Prof Petrylak said: "These results show that PSMA ADC has anti-tumour activity in patients who have failed up to two prior chemotherapies and hormone therapy. We have initiated a phase II trial of up to 75 patients in which the recommended dose will be 2.5 mg/kg. This new trial will evaluate responses in PSA and CTC; it will evaluate control of metastases in bone, internal organs and lymph nodes; and it will look at the effect on pain. Safety also will be assessed.
"The fact that this new targeted therapy is active against the most advanced forms of prostate cancer is encouraging, as few or no therapeutic options are available at present."
Professor Stefan Sleijfer, the scientific chair of the EORTC-NCI-AACR Symposium, from Erasmus University Medical Centre (The Netherlands), commented: "The approach tested here represents a novel way to treat prostate cancer. The anti-tumour effects already seen at such an early phase of clinical testing, such as a fall in circulating tumour cells, render this drug a promising compound for prostate cancer."
More information: Abstract no: 244. Proffered papers, plenary session 6, 15.00 hrs, Thursday 8 November.
Provided by ECCO-the European CanCer Organisation
- New drug targets vitamin D receptors in hormone resistant prostate cancers Nov 18, 2010 | not rated yet | 0
- Early clinical data show galeterone safe, effective against prostate cancer Apr 01, 2012 | not rated yet | 0
- Hormone inhibitor promising for hard-to-treat prostate cancer Jul 08, 2007 | not rated yet | 0
- New treatment hope for prostate cancer Feb 06, 2009 | not rated yet | 0
- Cabazitaxel with radiation and hormone therapy may improve prostate cancer survival Jan 12, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
2 hours ago From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
18 hours ago I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...
Cancer 14 hours ago | not rated yet | 0
(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...
Cancer 14 hours ago | not rated yet | 0 |
A new review finds cancer survivors suffer a diverse and complex set of impairments, affecting virtually every organ system. Writing in CA: A Cancer Journal for Clinicians, Julie Silver, M.D., associate professor at Harvar ...
Cancer 19 hours ago | not rated yet | 0
(AP)—A California doctor has been sentenced to 14 years in federal prison for bilking her patients out of more than $1 million by promising that an herbal supplement could cure late-stage cancer and other diseases.
Cancer 19 hours ago | not rated yet | 0
A new oral targeted drug, idelalisib (GS-1101), has the potential to stave off the need for additional treatments for relapsed or treatment-resistant chronic lymphocytic leukemia (CLL), according to a study led in part by ...
Cancer 21 hours ago | not rated yet | 0 |
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
3 hours ago | not rated yet | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
4 hours ago | not rated yet | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
15 hours ago | not rated yet | 0 |
(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...
16 hours ago | 3.7 / 5 (3) | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
13 hours ago | 3.7 / 5 (3) | 0 |
In order to avoid harms associated with alcohol consumption, in 2009 the National Institute on Alcohol Abuse and Alcoholism issued guidelines that define low-risk drinking. These guidelines differ for men and women: no more ...
13 hours ago | not rated yet | 0 |