Zometa and bone mets - 1247426

apra
Posts:142

Hello everyone,

There was a discussion on Inspire about Zometa and Xgeva and their ability to kill cancer cells instead of just strengthening the bones.

I would like to know whether these Bisphosphonate do kill cancer cells in the bones and whether they also contribute to lessening the degree of bone pain.

I would also like to know whether they cause toothache.

Thank you for your concern.

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Reply # - August 29, 2012, 06:27 AM

catdander
Posts:

Hi Apra, I am so sorry to read that your husband is in such pain. I hope he gets to see the onc while in Dehli.

Most if not all the current work being done on improving survival is on breast cancer and isn't suggestive of zometa's effects on lung cancer.

What is known for sure is that they can decrease that risk of developing pain and the risk of fracture (which by the nature of a risk, may or may not happen), can be reduced or delayed. Dr. Sanborn wrote about it here,
http://cancergrace.org/cancer-101/2009/04/14/rs-bone-met-mgmt-bisphos/

She says about tooth pain, "While doctors cannot reliably predict those patients who will develop ONJ, the risk is higher in patients who have bad teeth, chronic mouth infections, or who may require dental work while receiving the drug. The risk also increases the longer a person has been on the drug."

Dr. Sanborn says about improving overall survival, "Recently though, the New England Journal of Medicine published a randomized trial of patients with surgically-removed breast cancer who received endocrine therapy with or without Zometa. For the 1803 patients enrolled in this study, the addition of Zometa (given every 6 months for 3 years) improved disease-free survival (the time until cancer recurs) by 3.2%.
It is important to keep in mind that this was a trial of patients with resected breast cancer, and the results cannot be extrapolated to other cancers. These results help to support the rationale for further study in other tumor types and ongoing research and raises the question of whether bisphosphonates may improve outcomes beyond the risk of skeletal complications."

My thoughts are with you and your husband today,
Janine

I'm not sure but you may need to log off Grace to access this list of links, maybe depending on your browser. http://cancergrace.org/search-results?q=Bisphosphonates (please let me know, fmi)

Reply # - August 29, 2012, 07:56 AM

apra
Posts: 142

Janine,

Thank you so much. I have accessed the links but will read them again. Dr. West spoke about some trials that were ongoing in 2007 to look at the feasibility of getting Zometa infusions 2 - 6 times a year instead of once every 3-4 weeks as it was believed this might provide the same benefits.

I would like to know the results of this trial if it was completed and what is the current thought on the frequency of giving Zometa infusions.

In the light of ONJ, I read somewhere that the Bisphosphonate stays in our system for almost 15 years, and therefore stopping the Bisphosphonate after ONJ occurs does not give much relief although ofcourse the drug has to be stopped. So if the drug remains in your system this long, will it not be better to go for longer gaps like it is done for breast cancer according to Dr. Sandborn's article above?

Ofcourse if the patient gets it once in every 3-4 weeks the volume of sales of the drug will increase. I sincerely hope that this is not the only reason for sticking to the present frequency protocol :(.

Reply # - August 29, 2012, 08:30 AM

catdander
Posts:

I don't think anything new is known about the interaction with lung cancer. The link with the list of results has many forum responses from doctors some within the last few months on the matter. Did the inspire discussion give any trial info?

While searching for answers earlier, I read a post from Dr. West stating there is a lot of room between giving a full dose and nothing at all. I took that as alluding to a less frequent schedule.

Reply # - August 29, 2012, 09:23 AM

Dr Pennell
Posts: 139

Bone metastases are a huge problem in lung cancer, with more than a third of advanced NSCLC patients experiencing them sometime in the course of their illness. They cause pain, poor quality of life (QOL), and fractures which can sometimes spell the end of independence for patients with an already shortened lifespan.

Agents like zometa and denosumab have both been proven to delay and reduce skeletal-related events (SREs) such as bone pain, need for radiation, and fracture, and so in my opinion should be part of routine care for most NSCLC patients with bone metastases. Denosumab, although more expensive than zometa, has some advantages in that kidney function is not important (as it is for zometa), and in head to head comparison with zometa denosumab showed a delay in time to first SRE.

So we know they help QOL in NSCLC patients, but do they actually treat the cancer itself? Well, we know that in experimental systems (cells in a dish or a mouse) that they can affect the ability of cancer to spread to the bone, and have some ability to kill tumor cells in a dish. Denosumab in particular seems to affect the bone "environment" in such a way that it prevents cancer cells from being able to spread to bone and establish metastases.

Intriguingly, in the head to head comparison of denosumab versus zometa in cancer pts (40% of which had lung cancer), an unplanned look at patient survival showed that lung cancer patients treated with denosumab actually lived significantly longer than pts on zometa. Since this was looked at after the fact it is not "proof" than denosumab somehow affects lung cancer survival, but it is consistent with effects seen in other diseases like breast cancer. I for one use a lot of denosumab, since it is at least as good as zometa while being no more toxic, but may be better.

A good, freely-available review on this topic is here: Bone matters in lung cancer

Reply # - August 29, 2012, 09:36 AM

Dr Pennell
Posts: 139

Oh, and as to how often to give it... The trials testing these drugs gave them every 3-4 weeks to line them up with the chemotherapy being given. They were continued indefinitely, so there really in no information about when it is OK to stop them or if it is OK to give them less often. For bisphosphanates like zometa, as someone pointed out they stay in the bone for a long time, so there is no real scientific rationale for giving them frequently and indefinitely. I personally usually line the treatments up to happen when the patient is here for something else: if chemo every 3 weeks, then give every 3 weeks. If the patient in on observation every 2 months, then given every 2 months. Is this OK? No data, but I think it probably is.

Reply # - August 29, 2012, 06:09 PM

Dr West
Posts: 4735

I agree completely on the timing and duration issues. I follow the same general guidelines of not necessarily having people do monthly just because you can do that. The companies that make and sell these drugs don't have any incentive to determine how infrequently they can be given and still be helpful, so we're left to our judgment. I think many experts favor the approach Dr. Pennell offered of treatment over a longer interval, and in fact I also follow the monthly x 3 months, followed by quarterly schedule for many patients.

-Dr. West

Reply # - August 30, 2012, 03:05 AM

apra
Posts: 142

Thank you every one. You are all treasures, and I'm glad you are not hidden treasures:).

Dr. Pennel, the statements made about Bisphosphonates was so helpful. I am glad that there is evidence that Denosumab gives longer survival to patients. Whatever extends life and improves QOL is welcome. However in India Denosumab is not available yet.

I wonder about the statement made in the previous linked article where it was said that the chances of developing ONJ was slightly higher with Denosumab.

My husband needs to have his tooth extracted, if not all the tooth then a small part that is hanging loose due to the failed root canal treatment. His onc says it is ok since he has not had the drug for about four weeks. We are really wondering what to do.

Thank you Dr. West for sharing your practice. We are going to talk to the onc about this and get Zometa in less frequent intervals.

Reply # - August 30, 2012, 08:17 AM

Dr Pennell
Posts: 139

This is a difficult situation in terms of knowing the risks. We know that any dental procedure (other than fillings, etc) increases the risk of ONJ, and I think it is the right thing to do to hold the zometa if a procedure has to happen, but I would have to say that there still is some risk at the bisphosphonates hang around in the bone long after infusions have stopped. However, this situation comes up frequently and there usually isn't a good alternative. If dental surgery or an extraction needs to be done, it needs to be done and all we can do is explain that there is some risk and watch out afterward for ONJ.

Reply # - August 30, 2012, 08:52 AM

apra
Posts: 142

Dr. Penell and Dr. West,

How often have you dealt with cases of ONJ in your practice?

I think Janine's husband had a tooth extracted after having been on Bisphosphonates. There must be some fortunate ones.

I believe Bisphosphonates can also cause toothache requiring dental work.

This business of trying to decide on the lesser evil is really getting me down, to extract or not to extract? To continue with Zometa or to leave it because of the fear of ONJ? Is ONJ reversible? I think not :(

I wonder how you doctors do it day after day for so many people. I think being an oncologist is so much more challenging than being a doctor in any other discipline. God bless you and continue to empower you.

Reply # - August 30, 2012, 04:54 PM

Dr West
Posts: 4735

I have had two patients over the past decade who had what appeared to be very early ONJ, identified very quickly, and both had improvement back to baseline over a few months, if even that. However, ONJ isn't always reversible.

The only thing I'd say about extraction vs. bisphosphonate therapy is that just having the need for an extraction is a significant risk factor, so just holding off on the procedure itself isn't protective when someone is receiving medications that are associated with a risk of ONJ.

-Dr. West

Reply # - August 30, 2012, 11:45 PM

apra
Posts: 142

At the risk of sounding absolutely stupid, but because I'm trying to grab at any stray straw of hope, Dr. West, what would you say are the very early signs of ONJ :-?

Your comment

'The only thing I’d say about extraction vs. bisphosphonate therapy is that just having the need for an extraction is a significant risk factor, so just holding off on the procedure itself isn’t protective when someone is receiving medications that are associated with a r

isk of ONJ.'

I realise now that our holding off the tooth extraction may not be such a helpful idea. We thought we were protecting him from ONJ. I though that he tooth extraction would act like a trigger for the ONJ. Mabe that's not how it is after all.

I believe not everyone on Bisphosphonates who need a tooth extraction and who get the tooth extracted develops ONJ. :) :-?

Your answer has lifted a heavy cloud off our mind. Our onc said to get the tooth extracted, but he did not tell us that not getting the tooth extracted was also not protecting us from ONJ.

Thank you so much.

Reply # - August 31, 2012, 08:29 AM

catdander
Posts:

Apra, sorry I'm so late entering back to the conversation.
My husband's onc follows his case with PET scans. On one of them was found some suv uptake in his jaw. At that point he was taken off zometa. I did a lot of reading and I went to the dentist with him. He had irritation and inflammation (the cause for suv uptake) to a tooth that had lost its crown a year earlier. The dentist didn't know as much about IV zometa as I'd thought she would (she does now :wink: ). The problem was taken care of and not heard from again.
One thing we did change about his oral hygiene is he uses PerioRx (chlorhexidine Gluconate oral rinse, 0.12%). It's the rinse all my dentists have used in the office for as long as I know. In the US I can buy it at the dentist office. It's been a while since I searched for info on ONJ but as I recall this rinse was the one common treatment across everything I read.
Almost no one gets ONJ even if they do need dental work.

Let us know how your husband's scans go
Best of luck,
Janine

Reply # - August 31, 2012, 08:43 AM

apra
Posts: 142

Janine, thank you for coming back. I just remembered about your husband's dental procedure which I read somewhere on Grace (so you see, I do browse the archives :-D).

Did he have a tooth extracted? If the crown came off, then it must have been a tooth which had ndergone root canal treatment. As you know, our dentist failed to crown my husband's teeth after the root canal and now it has cracked, necessitating extraction.

How many months was your husband off the Zometa before he underwent the dental work? I know everyone is different, but just curious, please don't mind my questions.

Reply # - August 31, 2012, 09:48 AM

catdander
Posts:

I don't mind your questions. I know how difficult it is to find any info on ONJ. Because it is so rare progess on it's treatment hasn't made a lot of headway. It's good to hear Dr. West say he's only seen 2 cases in 10 years and both were mild.
D never had his tooth pulled. The dentist feels it is stable. She said it was an old kind of root canal process with a post put in. The post was the problem and now that it's been removed or cut down (don't remember which) it isn't being irritated. D didn't start back taking zometa because the spine met or probable spine met is no longer evident. I'm glad he had the opportunity to stop that treatment and one more worry to set aside.

Reply # - August 31, 2012, 05:03 PM

apra
Posts: 142

Janine, thank you for the detailed information. It's wonderful that the bone met was addressed by the treatments given. I think bone mets are the toughest mets in lung cancer. My husband is having partial response to Alimta. Previously too, the onc decided to go ahead with Almta infusions even if there was obvious progression in the bones. He said, as far as bone mets are concerned, we will continue to zap them with radiation and continue the therapy. I think that was a wrong strategy now.

I am still waiting for an answer from the doctors in my other thread on severe stomach pain. Perhaps I should have started a new thread because my question was about doing mutation tests from tissue/bone taken from iliac bone. Whether such procedure is possible. Because I read somewhere that once bone is taken out it has to be de mineralised and then sent for biopsy and mutation testing from bone tissue is not reliable. Whether.what I read still stands is what I would like to know.

Reply # - August 31, 2012, 06:53 PM

Dr West
Posts: 4735

Apra,

The early symptom of ONJ is jaw and/or gum pain.

Yes, you're correct that mutation testing is generally very challenging if not impossible when the DNA has been subjected to the chemicals that decalcify bone.

-Dr. West

Reply # - August 31, 2012, 09:35 PM

apra
Posts: 142

Thank you Dr. West,

As my husband only has toothache, I guess we can go ahead with the tooth extraction, if not full tooth extraction, then the part that is hanging out.

I just texted our onc about the concerns regarding bone biopsy. He has not replied yet. I hope he does not feel offended that I am brining out some cons in his plans.

I am also concerned about worsening bone pain if we go through this bone biopsy. He also said there is a slight increase of pleural effusion, so maybe we will ask about taking out the effusion and trying a biopsy on that.

Thank you and God bless

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