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In my most humble opinion among the most vital and impactful program in the world, which supports prostate cancer research funding and prostate cancer research resources, is in trouble. It is the only government program that funds only prostate cancer research. All of its research funding mechanisms are designed to fund high risk and potentially high return research, research that makes a major impact on out lives.

Shockingly, some members of the United States Senate have decided to take aim at our program. They are threatening to make major financial cuts, cuts that will affect your survival and your quality of life.

The PCRP has been, year after year, the leader in the development of our newest treatments. The next drug that will extend your life or the life of your loved one is being threatened. Don’t let this happen. We need this program intact.

The Senate is preparing to cut $16 million (20% of our budget) from our PCRP budget. Each year we ask for a budget increase and breath a sigh of relief when we are maintained at $80 million dollars (which is ½ of what is received for the DOD Breast Cancer Program). Now, they want to cut our budget. Now they want to cut short our life and fail to protect our quality of life.

This is not acceptable. We need to immediately let our Senate members known that cutting the Department of Defense Prostate Cancer Research Program is unacceptable. You, your partner, your children and your friends need to immediately make contact with your senators and demand that they stand firm and make sure that our budget is not cut.

The sad thing is that the House of Representatives which is usually the more aggressive budget cutting part of the legislature has already passed a resolution to continue the DOD PCRP’s budget for the fiscal year 2015 at the $80 million level.

The U.S. Senate is prepared to cut $16 million in critical research dollars – 20 percent of Prostate Cancer Research Program funding – from the 2015 federal budget.

The Department of Defense (DOD) plays a key role in the war on cancer, and the Prostate Cancer Research Program (PCRP) within the DOD has helped save countless lives by funding the discovery of three new and powerful prostate cancer treatments in the last three years.

Now is the time when we all must act. Each of us needs to make contact with your senators and press them to support the full funding for fiscal year 2014 of $80 million for the Prostate Cancer Research Program in the Department of Defense.



Joel T. Nowak, M.A., M.S.W.


Disclosure: I am a proud consultant to the DOD PCRP

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Yesterday’s post was about the use of chemotherapy (with docetaxel) for the treatment of men with advanced prostate cancer who were 80 years old or older. Today’s post is about the use of chemotherapy in men 60 years or younger. The research for both of these posts was performed by the same team of scientists in a multicenter retrospective study in Italy.

A large portion of prostate cancer is diagnosed in men over the age of 60 years so castration-resistant prostate cancer (CRPC) is rarely observed in men younger than 60 years.   As a result the clinical outcomes of these younger men have not been clearly defined. There is a common feeling of a worse prognosis for these younger men. In the study which is the topic of this post the aim is to assess the clinical outcomes of this specific population.

The researchers reviewed the clinical records of all the men younger than 60 with CRPC from participating institutions, treated with docetaxel (DOC), both in clinical trials and in clinical practice. They recorded the pre- and post-DOC clinical history, the DOC treatment details and outcomes.

As of the date of publication they have collected a consecutive series of information on 128 men from 24 Italian hospitalsThe median age was 57 (range 41 to 60). The median baseline prostate-specific antigen (PSA) was 85 ng/ml (range 1 to 3,020); 87% of the pts had bone metastases while 47%, 10%, and 13% showed nodal, liver and lung metastases, respectively.

All but 12 of the men received DOC with a 3 week standard schedule, the remaining being treated with a weekly, reduced dosage schedule.

A PSA reduction greater than 50% was observed in 61% of the the men; among the 86 men with measurable disease who underwent a radiological re-evaluation at the treatment end, four and 13 men achieved complete and partial response, respectively (response rate 20%).

The main grade 3-4 toxicities were anemia (five men), neutropenia (18 men), febrile neutropenia (one man), fatigue (five men), peripheral neuropathy (three men). The median progression-free survival (PFS) and overall survival (OS) were 7 months and 21 months, while the 1 year PFS and OS rates were 17.6% and 74.9%, respectively.

Their data seems to not confirm that younger men with CRPC have a worse prognosis compared to the older men since their survival outcomes and response rate are similar to those observed in general population of men with CRPC.

J Clin Oncol 32, 2014 (suppl 4; abstr 214); Antonello Veccia, Cinzia Ortega, Giuseppe di Lorenzo, Francesca La Russa, Salvatore Luca Burgio, Gaetano Facchini, Caterina Messina, Cosimo Sacco, Gilbert Spizzo, Michele Aieta, Michele Lodde, Giovanni Mansueto, Paolo A. Zucali, Alessandro D’Angelo, Roberto Iacovelli, Francesco Massari, Franco Morelli, Giuseppe Procopio, Fiorella Ruatta, Orazio Caffo, CYCLOP Study Group.

Joel T. Nowak, M.A., M.S.W.


Chemotherapy (chemo with docetaxel) has a reputation for being a difficult therapy loaded with many side effects.  I believe that this reputation is overblown given that all of our new non-chemotherapies (other than Provenge) come with their own list of significant side effects.  However, its reputation is in the minds of many, so men who are elderly will often choose to forgo chemo because of the age and comorbidities as well as an underlying cynicism around the possible survival advantages at this older age.

Is this the right decision?  Should older men 80 years and older have chemotherapy to treat their advanced prostate cancer?

A group of Italian researchers performed a retrospective study aimed to assess the clinical outcomes in this very elderly castrate resistant advanced prostate cancer (CRPC) population.

They reviewed a consecutive series of 115 men from 28 Italian hospitals with a median age was 82 (range 80 to 90) and a median baseline prostate-specific antigen (PSA) of 92 ng/ml (range 3 to 2,981); 83% of the men had bone metastases, while nodal, lung and liver metastases were observed in 39%, 9%, and 8% of the men respectively.

They found a PSA reduction greater than 50% in 55% of the men; an objective response was observed in 15% of the 60 men who underwent a radiological re-evaluation at the treatment end.

Grade 3-4 toxicities were: anemia (2%), neutropenia (10%) , thrombocytopenia (2%), fatigue (10%), diarrhea (4%), nausea (2%), renal (2%), and febrile neutropenia (2%). The median progression-free survival (PFS) and overall survival (OS )were 7 months and 20 months, while the 1 year PFS and OS rates were 21.2% and 71.5%, respectively.

This data suggests that a population of selected very older (age 80 and older) advanced prostate cancer survivors can safely have chemotherapy with a good toxicity profile. In this older population chemotherapy is able to produce survival outcomes comparable to pivotal trials (18

J Clin Oncol 32, 2014 (suppl 4; abstr 92); Antonello Veccia, Salvatore Luca Burgio, Giuseppe di Lorenzo, Cinzia Ortega, Florinda Scognamiglio, Michele Aieta, Fable Zustovich, Rodolfo Mattioli, Giovanni Mansueto, Gaetano Facchini, Giuseppe Procopio, Alessandro D’Angelo, Gilbert Spizzo, Maddalena Donini, Roberto Bortolus, Giovanni Vicario, Paolo A. Zucali, Umberto Basso, Giovanni Lo Re, Orazio Caffo, DELPHY Study Group

Joel T. Nowak, M.A., M.S.W.


In yesterday’s post I wrote about the possibility of looking for the presence of the splice variant ARV7 to determine if you would be resistant to enzalutamide (Xtandi).  Today I am going to expand on this issue and discuss an additional study that demonstrated that the presence of ARV7 in circulating tumor cells not only can predict initial resistance to Xtandi, but it also can predict resistance to abiraterone (Zytiga).

For the technical among us androgen receptor splice variant-7 (ARV7) is a truncated form of the androgen receptor that lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor.

Now to the bottom line findings without technical jargon- This study evaluated 31men treated with Xtandi and 31 treated with Zytiga.  Of the men treated with Xtandi, 38.7% had detectable ARV7 and in the Zytiga group 19.4% had detectable ARV7.

Among men receiving enzalutamide, AR-V7–positive men had inferior PSA response rates (0% vs 52.6%, P=0.004), PSA-PFS (median 1.4 vs 5.9 months, P<0.001), and PFS (median 2.1 vs 6.1 months, P<0.001) compared to AR-V7–negative men.

Similarly, among men receiving abiraterone, ARV7 positive men had inferior PSA response rates (0% vs 68.0%, P=0.004), PSA-PFS (median 1.3 months vs not reached, P<0.001), and PFS (median 2.3 months vs not reached, P<0.001).

CONCLUSION- The detection of ARV7 in circulating tumor cells in men with mCRPC is associated with resistance to both enzalutamide and abiraterone. We should ask our doctors to consider our ARV7 status as a potential biomarker to predict our resistance to AR-targeting agents like Xtandi and Zytiga to facilitate our treatment selection.  Yesterday’s study along with this one should fuel the development AR N-terminal domain inhibitors to short circuit this issue.

J Clin Oncol 32:5s, 2014 (suppl; abstr 5001); Emmanuel S. Antonarakis, Changxue Lu, Hao Wang, Brandon Luber, Mary Nakazawa, Yan Chen, Jeffrey C. Roeser, Helen L. Fedor, Tamara L. Lotan, Qizhi Zheng, Angelo M. De Marzo, John T. Isaacs, William B. Isaacs, Rosa Nadal, Channing Judith Paller, Samuel R. Denmeade, Michael Anthony Carducci, Mario A. Eisenberger, Jun Luo

Joel T. Nowak, M.A., M.S.W.


I have written a lot about how we need more data about the many new drugs we have to treat men with advanced prostate cancer.  The many questions that continue to swirl around us pertain to the development of cross resistance (taking one drug causes another to not work) between these new drugs, knowing the best order to take these drugs (sequencing), knowing what drugs might work and knowing when a drug is working and or has stopped working.

To work towards answering the question about when enzalutamide (Xtandi) might work for an individual researchers have performed an evaluation of Xtandi’s effects on cancer and on androgens in blood and bone marrow, as well as associate these with clinical observations.

In a prospective phase 2 study, 60 men with metastatic castrate resistant prostate cancer (mCRPC) and bone metastases were given Xtandi as well as bone marrow biopsies before treatment and at 8 weeks after beginning treatment.

They found that the median time to treatment discontinuation was 22 weeks and that twenty-two (37%) of the men exhibited primary resistance to Xtandi (discontinuing treatment within 4 months). They also found that the maximal prostate-specific antigen (PSA) decline of greater or equal to 50% and greater than or equal to 90% occurred in 27 men (45%) and 13 men (22%) respectively.

They found that the presence of an ARV7 variant (Androgen receptor splice variant-7 is a truncated form of the androgen receptor that lacks the ligand-binding domain).was associated with primary resistance to Xtandi (p=0.018).

Because of the limited numbers of men in the study, to be on the safe side additional validation of these findings need be performed.  However, if you are having difficulty in deciding if Xtandi is your next best choice for a treatment you should discuss this data with your doctor to see if it might make sense for you to see if you have a significant presence of ARV7.

Eur Urol. 2014 May 29. pii: S0302-2838(14)00415-1. doi: 10.1016/j.eururo.2014.05.005; Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, Tu SM, Aparicio A, Troncoso P, Mohler J, Logothetis C

PubMed Abstract
PMID: 24882673

Joel T. Nowak, M.A., M.S.W.