Interestingly, here is some other new information on Zometa (zoledronic acid).
There is this data that shows what genes are out of whack and what agents interfere with the cancer cells called Comparative Toxicogenomic Database.
You look up the cancer type..click on the hyperlinked gene and it will list the agents that impact those genes.
For example, this is the information for Zoledronic Acid
http://ctd.mdibl.org/detail.go?type=chem&acc=C088658&view=ixn&geneAcc=595
Forums
Re: Zometa vs Reclast
There are a lot of questions that have been introduced in this thread. I will try to answer a few (or at least give you my perspective). And I will refrain from any comments on pharma.
The most import question for everyone with myeloma is, why do we use bisphosphonates (Zometa [zolendronic acid] or Aredia [pamidronate])? Part of the answer is simple, these are medications that alter the balance of bone destruction and construction in favor of construction. Hence, the "bone builders" label.
The initial interest in the above listed bisphosphonates was that they would strengthen bones in patients with myeloma bone disease -- decreasing the risk of skeletal related events. Further, excitement was enhanced when preclinical data (in the lab and mice) suggested that they had anti-myeloma activities. This aspect, unfortunately, has not been consistently demonstrated in clinical trials.
So, based on clinical trial design we have empirically given bisphosphonates monthly for 2 years to patients with bone disease. After 2 years, patient and doctor discretion is utilized to maintain therapy -- every 3 months or so is how I typically manage bisphosphonate therapy. There is no magic to the dosing. To my knowledge, I cannot tell you that every other month dosing is better or worse that monthly etc.
Recently, the MRC Myeloma IX trial out of the United Kingdom compared Zometa and clodronate (Bonefos) (a third bisphophosphate) in almost 2000 myeloma patients (clodronate is not used in the US; Morgan et al Lancet 2010). The MRC IX study is notabe for a number of things and has changed how I utilize bisphosphonates in my patients.
The use of these drugs is not without risk. As I indicated above, osteonecrosis of the jaw is a risk although rare (and likely avoidable with careful management). These drugs can also affect kidney fucntion and can be associated with malaise or flu-like symptoms. Zometa tends to have a slightly higher risk of the above issues.
It is also important to note that with our increasing knowledge of the bone marrow microenvironment and the growth factors that control the balance between osteoblasts and osteoclasts (the cells that build bone and destroy bone, respectively), new agents are being developed to address bone diasease and skeletal related events in myeloma (and other diseases).
I am sure that I did not answer all of the questions, but I wanted to make sure that the basics were understood. Why we use bisphosphonates and why Zometa should be the preferred drug in most patients.
The most import question for everyone with myeloma is, why do we use bisphosphonates (Zometa [zolendronic acid] or Aredia [pamidronate])? Part of the answer is simple, these are medications that alter the balance of bone destruction and construction in favor of construction. Hence, the "bone builders" label.
The initial interest in the above listed bisphosphonates was that they would strengthen bones in patients with myeloma bone disease -- decreasing the risk of skeletal related events. Further, excitement was enhanced when preclinical data (in the lab and mice) suggested that they had anti-myeloma activities. This aspect, unfortunately, has not been consistently demonstrated in clinical trials.
So, based on clinical trial design we have empirically given bisphosphonates monthly for 2 years to patients with bone disease. After 2 years, patient and doctor discretion is utilized to maintain therapy -- every 3 months or so is how I typically manage bisphosphonate therapy. There is no magic to the dosing. To my knowledge, I cannot tell you that every other month dosing is better or worse that monthly etc.
Recently, the MRC Myeloma IX trial out of the United Kingdom compared Zometa and clodronate (Bonefos) (a third bisphophosphate) in almost 2000 myeloma patients (clodronate is not used in the US; Morgan et al Lancet 2010). The MRC IX study is notabe for a number of things and has changed how I utilize bisphosphonates in my patients.
- The authors demonstrated that the use of bisphosphonates (either) decreased skeletal related events in myeloma patients regardless of the observation of active bone disease at diagnosis.
- Further, Zometa reduced mortality by 16% as compared to clodronate extending the median overall survival by 5·5 months again relative to clondronate. (Note that this is not Aredia (pamidronate), but Bonefos (clodronate) that Zometa was compared to, so we cannot comment on whether there is a similar benefit of Zometa versus Aredia.)
- Based on the findings, I generally recommend initiation of monthly bisphosphonate therapy in all patients (following dental clearance to decrease incidence of osteonecrosis of the jaw). Zometa is the bisphosphonate that I prefer.
The use of these drugs is not without risk. As I indicated above, osteonecrosis of the jaw is a risk although rare (and likely avoidable with careful management). These drugs can also affect kidney fucntion and can be associated with malaise or flu-like symptoms. Zometa tends to have a slightly higher risk of the above issues.
It is also important to note that with our increasing knowledge of the bone marrow microenvironment and the growth factors that control the balance between osteoblasts and osteoclasts (the cells that build bone and destroy bone, respectively), new agents are being developed to address bone diasease and skeletal related events in myeloma (and other diseases).
I am sure that I did not answer all of the questions, but I wanted to make sure that the basics were understood. Why we use bisphosphonates and why Zometa should be the preferred drug in most patients.
-
Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Zometa vs Reclast
Additional comparative data for Zometa (zoledronic acid) vs. pamidronate (Aredia):
"In the overall patient population, zoledronic acid (4 mg) reduced the mean annual incidence of skeletal complications (skeletal morbidity rate) by 25% compared with pamidronate (1.04 events per year for 4 mg zoledronic acid vs. 1.39 events per year for pamidronate; p≤0.084). These reductions were significant in the hormonal therapy breast carcinoma stratum (0.83 SREs per year vs. 1.37 SREs per year, respectively; p≤ 0.039). The mean skeletal morbidity rate in the 4 mg zoledronic acid group consistently was lower compared with the pamidronate group in all patient strata and for all individual types of SREs (Table 4). These differences were significant in the overall patient population for radiation to bone (0.47 events per year for 4 mg zoledronic acid vs. 0.71 events per year for pamidronate; P 0.015).....snip
Treatment with 4 mg zoledronic acid reduced the risk of developing a skeletal complication by an additional 16% compared with pamidronate in the overall patient population (Fig. 3)"
http://university.asco.org/dgtfiles/ClassicReferences/Breast_RecurrentMetastatic%20Disease/2..pdf
"In the overall patient population, zoledronic acid (4 mg) reduced the mean annual incidence of skeletal complications (skeletal morbidity rate) by 25% compared with pamidronate (1.04 events per year for 4 mg zoledronic acid vs. 1.39 events per year for pamidronate; p≤0.084). These reductions were significant in the hormonal therapy breast carcinoma stratum (0.83 SREs per year vs. 1.37 SREs per year, respectively; p≤ 0.039). The mean skeletal morbidity rate in the 4 mg zoledronic acid group consistently was lower compared with the pamidronate group in all patient strata and for all individual types of SREs (Table 4). These differences were significant in the overall patient population for radiation to bone (0.47 events per year for 4 mg zoledronic acid vs. 0.71 events per year for pamidronate; P 0.015).....snip
Treatment with 4 mg zoledronic acid reduced the risk of developing a skeletal complication by an additional 16% compared with pamidronate in the overall patient population (Fig. 3)"
http://university.asco.org/dgtfiles/ClassicReferences/Breast_RecurrentMetastatic%20Disease/2..pdf
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Zometa vs Reclast
OTOH when it comes to ONJ...pamidronate is better agent.
"The type of bisphosphonate also seems to represent a significant risk factor in the development of ONJ. We observed only one case of ONJ in patients treated with pamidronate alone, while all other cases were associated with the use of zoledronic acid either alone or in combination with pamidronate or ibandronate....snip
....The cumulative hazard of developing ONJ was significantly higher in patients treated with zoledronic acid alone than in those treated with pamidronate alone/pamidronate+zoledronic acid/zoledronic acid+ibandronate sequentially (1% at 1 year and 15% at 4 years vs. 0% and 5%, p=0.003). In conclusion, the risk of ONJ is increased with time of exposure and probably with the use of zoledronic acid....snip
.....Although we discontinued bisphosphonates after the development of osteonecrosis, no improvement was observed. This underlines the importance of prevention of this complication and suggests that the decision concerning further treatment should be mainly based on the derived or expected benefit. Discontinuing bisphosphonates leads to a marked increase in bone resorption, which can lead to an increased risk of bony complications. In conclusion, ONJ is a complication of bisphosphonate treatment, associated with the time of exposure to this treatment in patients with multiple myeloma. The risk appears to be higher with zoledronic acid than with pamidronate"
http://haematologica.com/content/91/7/968.full.pdf
"The type of bisphosphonate also seems to represent a significant risk factor in the development of ONJ. We observed only one case of ONJ in patients treated with pamidronate alone, while all other cases were associated with the use of zoledronic acid either alone or in combination with pamidronate or ibandronate....snip
....The cumulative hazard of developing ONJ was significantly higher in patients treated with zoledronic acid alone than in those treated with pamidronate alone/pamidronate+zoledronic acid/zoledronic acid+ibandronate sequentially (1% at 1 year and 15% at 4 years vs. 0% and 5%, p=0.003). In conclusion, the risk of ONJ is increased with time of exposure and probably with the use of zoledronic acid....snip
.....Although we discontinued bisphosphonates after the development of osteonecrosis, no improvement was observed. This underlines the importance of prevention of this complication and suggests that the decision concerning further treatment should be mainly based on the derived or expected benefit. Discontinuing bisphosphonates leads to a marked increase in bone resorption, which can lead to an increased risk of bony complications. In conclusion, ONJ is a complication of bisphosphonate treatment, associated with the time of exposure to this treatment in patients with multiple myeloma. The risk appears to be higher with zoledronic acid than with pamidronate"
http://haematologica.com/content/91/7/968.full.pdf
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Zometa vs Reclast
Thanks for the follow-up information, suzierose.
I think the issue with Zometa causing more osteonecrosis of the jaw is a common finding. In the trial that compared Zometa with Bonefos in myeloma patients, I believe the risk of developing ONJ was about 3x or 4x higher in the Zometa patients than in the Bonefos patients (about 4 percent in the Zometa-treated patients and about 1 percent in the Bonefos patients, if I recall correctly).
That said, the methods for preventing ONJ have advanced a lot even in the past few years, so it probably shouldn't be as big a concern as it was, say, 5 years ago.
The difference in ONJ rates between Zometa and Aredia (pamidronate) and Zometa and Bonefos got me wondering if, in general, side effects occur more frequently with Zometa than with the other drugs. But, if you look at the side effect data reported in the Cancer article from 2003 that you linked to, the frequency of side effects among patients treated with Zometa and Aredia are pretty much the same.
So whatever makes Zometa more effective at preventing skeletal events and (possibly) extending survival of myeloma patients may be the same thing that makes it more likely to cause ONJ.
I think the issue with Zometa causing more osteonecrosis of the jaw is a common finding. In the trial that compared Zometa with Bonefos in myeloma patients, I believe the risk of developing ONJ was about 3x or 4x higher in the Zometa patients than in the Bonefos patients (about 4 percent in the Zometa-treated patients and about 1 percent in the Bonefos patients, if I recall correctly).
That said, the methods for preventing ONJ have advanced a lot even in the past few years, so it probably shouldn't be as big a concern as it was, say, 5 years ago.
The difference in ONJ rates between Zometa and Aredia (pamidronate) and Zometa and Bonefos got me wondering if, in general, side effects occur more frequently with Zometa than with the other drugs. But, if you look at the side effect data reported in the Cancer article from 2003 that you linked to, the frequency of side effects among patients treated with Zometa and Aredia are pretty much the same.
So whatever makes Zometa more effective at preventing skeletal events and (possibly) extending survival of myeloma patients may be the same thing that makes it more likely to cause ONJ.
Re: Zometa vs Reclast
Hi Susierose,
You seem to be quite knowledgable about Reclast and Zometa. Can you tell me where you get your information about the two drugs, especially the concentration? You say that Reclast contains 5mg of zoledronic acid per 100 ml and that Zometa contains 4 mg zoledronic acid per per 5 ml. I think you are absolutely correct, but my oncologist insists that the two drugs are identical. Agreed they contain the same active ingredient, but it appears to me that Zometa is about 20 times stronger than Reclast. He is insisting on Reclast and I think he is wrong. I need a source for the concentration information that I can show him. I think he is about to prescribe the wrong drug (Reclast) for me since I have Multiple Myeloma and osteoporesis.
You seem to be quite knowledgable about Reclast and Zometa. Can you tell me where you get your information about the two drugs, especially the concentration? You say that Reclast contains 5mg of zoledronic acid per 100 ml and that Zometa contains 4 mg zoledronic acid per per 5 ml. I think you are absolutely correct, but my oncologist insists that the two drugs are identical. Agreed they contain the same active ingredient, but it appears to me that Zometa is about 20 times stronger than Reclast. He is insisting on Reclast and I think he is wrong. I need a source for the concentration information that I can show him. I think he is about to prescribe the wrong drug (Reclast) for me since I have Multiple Myeloma and osteoporesis.
-
Lizard_Lips - Who do you know with myeloma?: Me
- When were you/they diagnosed?: September, 2007
Re: Zometa vs Reclast
Aredia has been around much longer than Zometa and that is why it is now available as a generic. I talked to my Oncologist about Aredia, as that is what he has me on. He told me that the first real break through in "new" drugs that benefited patients was when Aredia was introduced. It helps prevent and heal bone lesions. Patients that went on it had great results. It does not have any anti multiple myeloma benefits but was and is an important drug in healing some of the damage caused by the disease. Zometa does much the same but has some anti-MM benefits. Aredia takes longer to infuse - up to 2 hours. There are far fewer reported side effects with Aredia and a lot more people have been on it. My oncologist is still considering whether to switch some of his patients from Aredia to Zometa but isn't yet convinced that the benefits outweigh the cost of the drug.
Ron
Ron
-
Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Zometa vs Reclast
Hi Lizard_Lips,
You can find information about the concentration of both Reclast and Zometa on the front page of the websites for the two drugs,
http://www.reclast.com
http://www.us.zometa.com
If you look at the upper left corner on both websites, you'll see the concentration of the medications under the brand name.
For Reclast, the concentration is listed as 5mg / 100 ml. For Zometa, the concentration is 4mg / 5 ml.
Regarding the supposed "anti-myeloma" benefits of Zometa ... Granted, there was a major European clinical trials that showed a survival advantage for patients taking Zometa versus another, weaker, drug (Bonefos/clodronate) that was never approved in the U.S.
However, that trial never demonstrated that the survival benefit was due to the drug having an actual anti-myeloma effect like, say, myeloma drugs such as Velcade, Revlimid, or thalidomide. I also don't think you will find anything in the FDA-approved information for Zometa that says the drug has an anti-myeloma effect.
You can find information about the concentration of both Reclast and Zometa on the front page of the websites for the two drugs,
http://www.reclast.com
http://www.us.zometa.com
If you look at the upper left corner on both websites, you'll see the concentration of the medications under the brand name.
For Reclast, the concentration is listed as 5mg / 100 ml. For Zometa, the concentration is 4mg / 5 ml.
Regarding the supposed "anti-myeloma" benefits of Zometa ... Granted, there was a major European clinical trials that showed a survival advantage for patients taking Zometa versus another, weaker, drug (Bonefos/clodronate) that was never approved in the U.S.
However, that trial never demonstrated that the survival benefit was due to the drug having an actual anti-myeloma effect like, say, myeloma drugs such as Velcade, Revlimid, or thalidomide. I also don't think you will find anything in the FDA-approved information for Zometa that says the drug has an anti-myeloma effect.
18 posts
• Page 2 of 2 • 1, 2