Zometa to high risk men with no bone metastases does not delay bone metastases appearing

[JimJimJimJim]

Jim Marshall (not a doctor) said ...

When prostate cancer moves out to new places in the body it is called metastatic prostate cancer. The new cancers are called metastases. 

 

When prostate cancer does spread, it prefers bone (in about 90% of cases). These new cancers in the bone are prostate cancer, not bone cancer. They most often occur first in the bones near the prostate - the hips and spine.

 

As the cancer eats into the bones, it causes two major problems - pain and bone damage.

 

Damaged bones can collapse or break. For the bones in the spine that hold us up and protect our spinal cord (vertebrae), collapsing can mean both enormous pain and the loss of control of our bodies below the collapse.

 

Zometa (zoledronic acid), when given to men with bone metastases, has been shown to both

delay damage to bones; and

extend life.

 

We covered the research showing this here:

Zometa to protect bones reduces skeletal related events, extends life

 

The hope was that if men at high risk took Zometa BEFORE bone metastases appeared, it may prevent or delay the appearance of bone metastases.

 

In the ZEUS trial (involving more than 1000 men), half the men at high risk got Zometa, and the other half none

 

Unfortunately, Zometa given early did not delay the appearance of bone metastases. 

 

So it seems that Zometa only helps AFTER bone metastases appear.

... end Jim

 

Eur Urol. 2014 Feb 20. pii: S0302-2838(14)00133-X. doi: 10.1016/j.eururo.2014.02.014. [Epub ahead of print]

Prevention of Bone Metastases in Patients with High-risk Nonmetastatic Prostate Cancer Treated with Zoledronic Acid: Efficacy and Safety Results of the Zometa European Study (ZEUS).

Wirth M1, Tammela T2, Cicalese V3, Gomez Veiga F4, Delaere K5, Miller K6, Tubaro A7, Schulze M8, Debruyne F9, Huland H10, Patel A11, Lecouvet F12, Caris C11, Witjes W13.

Author information

 

 

Abstract

BACKGROUND:

Patients with high-risk localised prostate cancer (PCa) are at risk of developing bone metastases (BMs). Zoledronic acid (ZA) significantly reduces the incidence of skeletal complications in castration-resistant metastatic PCa versus placebo.

OBJECTIVE:

To investigate ZA for the prevention of BMs in high-risk localised PCa.

DESIGN, SETTING, AND PARTICIPANTS:

Randomised open-label multinational study with patients having at least one of the following: prostate-specific antigen ≥20 ng/ml, node-positive disease, or Gleason score 8-10.

INTERVENTION:

Standard PCa therapy alone or combined with 4mg ZA intravenously every 3 mo for ≤4 yr.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

BMs were assessed using locally evaluated bone-imaging procedures (BIPs), with subsequent blinded central review. Patients with BMs, time to BMs, overall survival, and adverse events were compared between treatment groups.

RESULTS AND LIMITATIONS:

A total of 1393 of 1433 randomised patients were used for intention-to-treat (ITT) efficacy analyses, with 1040 patients with BIP-BM outcome status at 4±0.5 yr. The local urologist/radiologist diagnosed BIP-BMs in 88 of 515 patients (17.1%) in the ZA group and 89 of 525 patients (17.0%) in the control group (chi-square test: p=0.95), with a difference between proportions of 0.1% (95% confidence interval [CI], -4.4 to 4.7) in favour of the control group. In the ITT population (n=1393), the Kaplan-Meier estimated proportion of BMs after a median follow-up of 4.8 yr was 14.7% in the ZA group versus 13.2% in the control group (log-rank: p=0.65). Low hot spot numbers on bone scans were confirmed as metastases with additional imaging. Central reviews of BIPs were possible only on a subset of patients.

CONCLUSIONS:

ZA administered every 3 mo was demonstrated to be ineffective for the prevention of BMs in high-risk localised PCa patients at 4 yr.

PATIENT SUMMARY:

Zoledronic acid administered every 3 mo was demonstrated to be ineffective for the prevention of bone metastases in high-risk nonmetastatic PCa patients at 4 yr.

TRIAL REGISTRATION:

The ZEUS trial is registered in the Dutch trial register www.trialregister.nl and the ISRCTN register at http://www.controlled-trials.com/ISRCTN66626762.

Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Androgen deprivation therapy, Anticancer agents, Bisphosphonates, Bone metastases, Prostate cancer, Skeletal-related events, Zoledronic acid

PMID: 24630685

 

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

 

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.

[Paul Edwards]

Dr. Philip Saylor of Massachusetts General Hospital in Boston, provided expert commentary on the Medscape web site about the ZEUS trial:

 

“The ZEUS results affirm that we are well served to reserve the use of potent osteoclast inhibition — with either zoledronic acid or denosumab — for men with prostate cancer that is already metastatic to the bone and has progressed on first-line androgen-deprivation therapy.

 

Rather than preventing bone metastasis, zoledronic acid and denosumab have both been shown to significantly reduce the incidence of skeletal events, such as pathologic fractures and spinal cord compression, in prostate cancer patients with advanced disease..............

 

The clinically meaningful prevention of bone metastases will require agents that target the tumor and/or the bone microenvironment in some way that is distinct from osteoclast inhibition.”