Hello Dr. West and the Grace Community,
I am writing in order to get your opinion on my mother's treatment options after being on Iressa for 15 months with good response (since June 2013) only to find out today that her scans last week showed progression. Here are the results of the CT Scan:
- Small new sclerotic foci are now identified within the bodies of T1 and T2 veretebrae, T5 vertebral lesion remains unchanged
- multiple additional tiny new nodular pulmonary opacities are identified within the Right lower lobe and also within the Right upper lobe
- new nodular opacities are also identified left upper and lower lung fields
- this suggests new metastatic lesions
- the pleural-based nodular opacity in the left upper lung field is larger than previous measuring 7 x 4.5mm, previously 3.6 x 2.7mm
- an enlarging left celiac axis node is suspected, 1.3 x 0.9 cm
Given this information, the medical oncolgist suggested that these results are concerning and gave us 2 options:
1) continue on Iressa and follow up with CT scans in 2 months time. If continues to progress, then stop Iressa and start Cisplatin/Alimta.
OR
2) stop Iressa now and start Chemo with Cisplatin/Alimta.
The medical oncologist told us that her personal recommendation would be #1, to continue Iressa to try to get out more benefit and check back in 2 months time.
My question is: given the results of the CT scan, do you think that my mom should opt for the Chemo route?
Given the possible option for AZD9291 or CO-1686, I asked the oncologist if these agents are an option, she said that these are experimental agents and she can not comment on whether my mom should try them out or not. She said chemo is standard care and she is comfortable giving my mom chemo after the 2 months wait, but if we want she would be okay with my mom enrolling in a Phase 3 trial, not a Phase 1 or 2.
Reply # - October 2, 2014, 05:42 PM
During the meantime of being
During the meantime of being on Iressa for another 2 months, we were planning on using this time to get my mom on a trial with either AZD9291 or CO-1686 trial (it would probably take around this time given she would need to go through a biopsy and wait for results, followed by a washout period). Do you think this is a good plan? Or do you think my mom should opt for immediate chemotherapy to try to stop the cancer from further spreading?
Are there any other options that we have not thought of yet that we should consider?
My mom is 56 years old, asian, non-smoker. We live in Toronto, ON Canada. Looking forward to hearing back with your thoughts.
Sincerely,
William
Reply # - October 2, 2014, 10:27 PM
There are many ways to manage
There are many ways to manage acquired resistance, but the first branch point is to determine whether progression is just detectable or is clinically significant. That is in the eye of the beholder, but most experts are very comfortable having patients continue on an EGFR TKI beyond the time of earliest detected progression if a patient is tolerating it well and demonstrating only mild progression.
At the point at which clinically significant progression is noted, it's fair to ask whether it is only in a single location, in which case focal radiation or surgery is sometimes considered, or the more common situation of several areas of (or quite diffuse) progression. If progression is more widespread, many lung cancer specialists would now favor getting tissue to test for the presence of a T790M mutation and, if present, would favor pursuing a trial of either AZD9291 or CO-1686 if one is within reach. Many experts would NOT feel that a trial needs to be a phase 3 clinical trial to be worth pursuing, as all of the patients who have benefited from these agents up to now have benefited from an earlier phase trial, and some have benefited very substantially.
Otherwise, it is always reasonable to transition to chemotherapy after progression on an EGFR TKI has become clinically significant and also multifocal. Cisplatin/Alimta (pemetrexed) is a very strong choice as a regimen in this setting, and we now have evidence that it seems to be preferable to not continue the EGFR inhibitor concurrent with the chemotherapy after acquired resistance has developed, as described here:
http://cancergrace.org/lung/2014/09/30/acquired-resistance-impress-esmo/
As for the timing of whether to continue on the same regimen or switch to something new, that's entirely in the realm of medical judgment, which means it's something that we can't answer. I would just reiterate that it is profoundly reasonable to hesitate before moving on if things are more stable than progressive.
Good luck.
Reply # - October 4, 2014, 08:41 AM
Dear Dr. West,
Dear Dr. West,
Thank you very much for your speedy and thoughtful response. Knowing many experts, including yourself, are comfortable having patients continue EGFR TKI beyond the first point of detectable progression is comforting to me and surely made my mom's day a bit brighter yesterday.
However, you did mention mild progression and clinically significant progression, which got me thinking on 2 points.
1. mild progression: given my mom's recent CT scan would you consider this in your best judgement to be mild progression or is it more progressive given her results indicated new lesions in several areas, including:
- new lesions within the right and left lung
- growth in size of the present pleural based tumor
- additional mets to T1-T3 vertebrae
Would it be considered minor since growth is still within the millimeter scale rather than centimeter, albeit the new lesions seem to be diffuse rather than a single spot?
2. clinically significant progression: for the past 1 month my mom has been having complaints of more pain (3-4/10 NPRS) and more consistent episodes of pain specifically in her left T-spine area. She has a hacking cough for the past month that persists after recovery from a flu/cold. Are these symptoms of concern that warrant immediate chemotherapy? Also my mom has reduced her level of physical activity because she gets more tired easily compared to before. My mom did not emphasize these symptoms with her oncologist during her appointment on Thursday, hence the oncologist mentioned that since my mom is responding well to it symptomatically, side effects are few and tolerable, hence we can continue for another 2 months time and monitor. We are just afraid that the cancer is not controlled at the moment with Iressa and delay in treatment to get on a trial may be too late? Knowing that there is not right or wrong answer, and no one can predict the future, I'm just wondering if you can comment on this and offer your advice on the matter.
Reply # - October 4, 2014, 08:57 AM
To give you an idea of our
To give you an idea of our thoughts at the moment:
Pros to waiting for trial:
- may extend survival for a longer period if test positive for T790M mutation and respond well to the AZD9291 or CO-1686, after which chemotherapy can be a later option
- delay need for chemotherapy, which is associated with harsher side effects that is generally not tolerated well
- starting chemotherapy now will exclude her from possibility of enrolling in trials that test AZD9291 or CO-1686, hence waiting for a trial first is more feasible
Cons to waiting for trial:
- cancer may be quite progressive and delay in chemo treatment now may result in multiple mets to other organs/sites
Looking forward to hearing back from you and once again thank you for all your help and advice. I'm a physiotherapy student currently on placement, but finishing up my program in a couple of weeks. I think your website is a godsend and an excellent resource to support those going through such a horrible time in their lives. I work in the surgical step down unit and have taken the liberty to share your website link to patients post-lung surgeries for cancer to spread the word and share such a wonderful resource available.
Reply # - October 4, 2014, 09:52 AM
I'm sorry, hain, but we're
I'm sorry, hain, but we're not allowed to give individual patient recommendations, which would include things like interpreting the significance of progression. That's really what a patient's oncologist/medical team is for. GRACE wants to be able to provide the thought process and the tools, but we should leave the very subjective judgments to the patient and their doctor.
You clearly understand the pros and cons of the decision, which is really what we need to struggle with every day. You can see that there's no clearly right or wrong answer and that even experts may differ in their judgment here.
Good luck.
-Dr. West
Reply # - October 5, 2014, 06:48 AM
Hello Dr. West,
Hello Dr. West,
Thank you for your reply. I understand GRACE cannot provide specific patient recommendations. In order to make an informed decision about treatment options would you be able to make a comment on the accuracy of these response rate etc. to your understanding? for example:
1) I read somewhere that IV Chemo has a response rate of 20-40% (i.e., only 20-40% of patients respond to therapy), median PFS is 5 months, with OS about 11 months, is this accurate? If not, what are the accurate figures?
2) Is the combination of Afatinib + Cetuximab an option worth pursing?
http://www.onclive.com/web-exclusives/Promising-Findings-for-AfatinibCe…
3) Is Afatinib mono-therapy worth pursing after first-line EGFR TKI failure?
4) are there any other options we have not considered?
Thank you for your reply in advance, looking forward to hearing back from you.
Reply # - October 5, 2014, 09:28 AM
Hi hain,
Hi hain,
1) The numbers you cite are certainly in the ballpark, but it is important to remember a couple of things. First, "response rate" is a term of art in which response is limited to patients whose cancer either disappears or shrinks by a specified rate, often 50 percent. As a result, stated response rates do not include those patients whose cancer shrinks by a lesser percentage, or those whose cancer remains stable, both of which are good results in stage IV lung cancer. Dr. Pennell has written a helpful post on response rates and stability: http://cancergrace.org/lung/2009/07/01/congratulations-your-tumor-is-st…
Also, though the median overall survival rate for stage IV lung cancer has not changed much (because there continue to be a percentage of patients whose cancer is very aggressive), the trend is for patients who exceed the median to live longer and longer.
2) There has been some enthusiasm for the Afatinib/Cetuximab combination, but it is by no means settled that it is an effective option, and the combined side effects can be quite challenging. Dr. West has written about this regimen: http://cancergrace.org/lung/2013/08/17/afatinib-for-acquired-resistance…
3) Though afatinib has been approved as first-line treatment for patients with an EGFR mutation, it has not shown impressive results for patients who have developed acquired resistance to another EGFR inhibitor such as Tarceva. http://cancergrace.org/lung/2013/08/17/afatinib-for-acquired-resistance… (includes more discussion of afatinib/cetuximab).
4) I think Dr. West covered the options pretty thoroughly in his post earlier in this thread.
Good luck with whatever choice is made.
JimC
Forum moderator
Reply # - October 5, 2014, 06:47 PM
Yes, not much to add, though
Yes, not much to add, though I'd say that different people prioritize the options differently. Jim really summarized the issues around chemo beautifully -- I think the key point is that the 20-40% number underestimates the proportion of patients who benefit from chemotherapy, and the other question is whether there is any alternative that is better. I'd say that afatinib alone definitely isn't. The approximately 7-8% response rate with afatinib after Iressa (gefitinib) or Tarceva (erlotinib) is no better than you'd typically see from just giving one of the other EGFR inhibitors again -- merely re-treating can give that paltry response rate. Honestly, there is no good reason, certainly no compelling evidence, to give afatinib single agent in the setting of acquired resistance, even though many people do.
Afatinib and cetuximab certainly looks provocative, but that's in just a few dozen patients at a handful of centers. The early results are intriguing and merit further study, but until that happens, I would not presume that the combination will be both effective and tolerable in a multicenter study of a large number of real world patients in routine clinical practice.
-Dr. West
Reply # - October 5, 2014, 07:33 PM
Hello JimC and Dr. West,
Hello JimC and Dr. West,
Thank you for your replies. The clarification on response rate certainly makes chemo more attractive as an option for treatment.
Currently, my mom seems to be having ups and downs - yesterday there were episodes of pain whereby she needed to take Tylenol to help. Today the pain seems to have subsided but the persistent coughing remains. I estimate that until she receives another form of effective therapy besides her current once daily Iressa, which seems to have acquired resistance, she will continue to have this persistent coughing. Besides that I hope waiting for a clinical trial is the right thing to do and that the cancer does not take a huge toll in the grand scheme of things. I'm glad the 10 year or so impasse to acquired resistance is finally being answered with third generation TKIs that have high potential, just the timing isn't the greatest as the only way to gain access to these agents are through clinical trials that are limited in number and require time and different hurdles to get through. I will try to keep you guys posted on the progress.
Sincerely,
Will
Reply # - October 5, 2014, 10:07 PM
Hi,
Hi,
I'm sorry for what you are going through.
I'm not a doctor, but my mom is in pretty much the same situation (Tarceva, acquired resistance). I just want to say that I *cry* that it was impossible for her to get into a trial for AZD9291 or CO-1686 because of too long travel time (2 days one way) and other obstacles with insurance and language. I do cry and I know that this and the lack of an expanded access program might have shortened her life.
I'd also re-read what Dr. West wrote in this post: <b>"If progression is more widespread, many lung cancer specialists would now favor getting tissue to test for the presence of a T790M mutation and, if present, would favor pursuing a trial of either AZD9291 or CO-1686 if one is within reach" </b>
Reply # - October 6, 2014, 12:39 PM
costica, thanks so much for
costica, thanks so much for your added info. It's so helpful to get input from someone going through similar process.
Will, I hope your mom finds an alternative or added treatment to combat the cancer. I imagine this has already been said but, as you noted above the wait time until treatment is important because a person can become too sick to handle further treatment.
A cough can be difficult to live with so managing it is important. Have you read this post? http://cancergrace.org/cancer-treatments/2009/05/09/managing-cough/
Janine
Reply # - October 6, 2014, 08:38 PM
Hello Costica and Janine,
Hello Costica and Janine,
Thanks for your suggestions and comments.
Costica, I'm sorry your mom was unable to access any trials for AZD or CO. I'm just curious, is this because she had previously been treated with chemotherapy and many studies require patients to be chemo naive? I know for my mom, ideally she would at least try chemo right now for her obvious progression (objectively through CT and bone scans, and subjectively through her constant coughing and self-reported pain from bone mets). However, many studies I searched preclude the possibility of trying chemo prior to inception of the trial.
Janine, thank you for your link. I think my mom's family doctor prescribed her some codeine so I will suggest to her she have some as needed if and when her cough worsens. If only she had cough minus the pain, then I could chalk it up to allergies but the pain is real and present until she receives some effective therapy like you mentioned.
Just a question: In the meantime of waiting on enrollment for a trial, I was thinking of the possibility of having my mom try naturopathic therapies such as either Mistletoe injections or High dose Intravenous Vitamin C. Does anyone have any suggestions or references that might argue against these form of complementary/alternative therapies when used in conjunction with Iressa? I was thinking it might be worth a try, if not effective then at least we tried, but I surely hope it does not cause worsening of cancer growth or jeopardize our chances at getting into one of the clinical trials.
Reply # - October 6, 2014, 09:02 PM
The trial for AZD9291 accepts
The trial for AZD9291 accepts patients treated with Tarceva and at most one platinum doublet. My mom could not access it because of the location, which would require to travel by plane to another country. One way takes more than 24 hours. The same holds for the trial from Clovis: they accept patients treated with chemo.
Reply # - October 6, 2014, 09:18 PM
There are no studies of these
There are no studies of these complementary therapies with Iressa (gefitinib). In fact, there is extremely little clinical research of a meaningful quality on these interventions at all. I don't recommend them for my own patients, but in the end, it comes down to whether you believe that an approach with no meaningful evidence to support it should be presumed to be beneficial or not. I don't, and I think they are at least as likely to be harmful as helpful. Especially when approaches like high dose vitamin infusions have been theorized to be beneficial against cancer for decades but have failed to produce any actual good evidence of benefit in all of that time, I consider that absence of favorable evidence to be very telling.
-Dr. West
Reply # - October 7, 2014, 04:18 PM
Hello everyone,
Hello everyone,
Costica, I hear that these agents have breakthrough status and might be made available as early as first or second quarter next year - so tell your mom to hang in there!
Dr. West, as always thank you for your opinion. When you put it the way you do, these complementary therapies do not seem very attractive or meaningful to pursue. Having said that, we will try to hold the fort without any of the above mentioned complementary therapies. We have an appointment for a US trial running the CO-1686, hopefully everything falls into place and the out of pocket cost associated with being in the trial does not become too much of a financial burden given we are from Toronto, ON Canada.
Best,
William
Reply # - October 7, 2014, 08:00 PM
Sounds reasonable, but I
Sounds reasonable, but I really should underscore, I am conveying my interpretation of the issue and not an answer based on evidence -- we just don't have evidence.
-Dr. West
Reply # - October 29, 2014, 08:54 PM
Hello Dr. West,
Hello Dr. West,
Currently my mom is waiting for a biopsy to be conducted next Thursday in Toronto where we live. It seems that my mom is a candidate for the CO-1686 agent and will be officially enrolled if her mutation test comes back positive for the T790M - this will take about another 3 weeks, so she will probably start taking this agent if all goes well by the end of November.
Since the last time I wrote to you, during the past couple of weeks my mom has been experiencing more thoracic pain, probably from her spinal metastasis. It seems as though as the days progresses, so does her symptoms that are related to her cancer:
- thoracic/upper back pain; comes and goes but worse at night; alleviates with extra-strength tylenol; difficulty because of pain from transferring from sit to lying on bed because of the need to rotate spine
- poor appetite, which seems to be contributing to her having more difficulty maintaining weight; previously she was about 108-110 lbs, now she is 103-105lbs
- reduced activity level; although she is still able to perform house work and ADLs
- some nights having a constant sleep is not possible
These symptoms were not present 1 month ago, which suggests to me that her cancer is progressing and that the Iressa she is currently on is not working.
Last week she had a brain MRI and Chest CT. The brain MRI was normal and her chest CT reported little change. Here are my questions:
1. I am very curious as to whether it is normal for her to have such contrast between subjective reported feelings and objective measures of change on CT, as the two do not seem to correlate?
2. We were told that my mom should try to hold on until the biopsy next week, followed by a 2 week wait until results for mutation test comes back, to see the oncologist for a possibility of radiation to the spine to alleviate some pain. Do you think it would be wise to consider asking for an earlier date to meet the oncologist to discuss these changes?
Reply # - October 29, 2014, 09:06 PM
(continued)...
(continued)...
3. We were told that my mom can still receive radiation in the interim while waiting or after biopsy if she needs it. Do you think it would be wise to consider radiation ASAP? Or, should she hold on until she starts the CO-1686 (if we are lucky) and see how she responds to this agent, in the event this agent can shrink her spinal tumors and mitigate the thoracic pain to become more tolerable? The line of reasoning is because last year prior to starting Iressa, my mom had experienced upper back pain (albeit less intense than now), but once she started Iressa, the pain completely went away and she was pain free for a year and a half until now.
4. I was thinking the pros and cons to radiation early vs holding off, and please do correct me if I am wrong in my line of thinking. Pros for starting early would be preventing a spinal compression fracture or other complications from spine mets. Cons to starting early is that there is only limited number of radiation a person can receive to one area because of toxicity/side effects? Cons starting early would not allow us to see if the CO-1686 can mitigate spinal pain, allowing us to hold off radiation for later down the road, if in fact it is true that an area can only be radiated a limited number of times?
4. Are there anything else that we should consider that we have not already? Any and all comments are very much appreciated.
I'm very sorry for the long read and questions, but I am just very disheartened and worried for my mom. I look forward to hearing back from you and thank you very much for your replies in advance.
Best regards,
Will
Reply # - October 30, 2014, 08:25 AM
Hi Will,
Hi Will,
I'm sorry to hear of your mom's increasing symptoms. In light of the scan results it sounds as though many if not all of these symptoms could be related to the spine metastases. Even appetite can be affected by the level of pain she is experiencing.
As far as the apparent disconnect between her scan findings and escalating symptoms, that would also point to the spine mets as the cause, since they would not be imaged as well on a chest CT as they would on an MRI of the spine.
Radiation is the treatment of choice for metastases that are causing great pain and are in a location such as the spine where the breakdown of bones can cause great injury. Although systemic therapy can be effective against cancer cells anywhere in the body, radiation can provide much faster relief from pain and can help prevent irreversible injury to bone structures such as the spine. If that damage occurs before systemic therapy has a chance to be effective, it may be too late to use radiation effectively. In addition, though her initial treatment with Iressa was quite effective and eliminated her pain, subsequent treatment regimens usually are not as effective so it is probably not realistic to expect the same kind of dramatic turnaround from chemo/targeted therapy.
The bottom line is that her symptoms should be reported to her doctor as soon as possible, so that he or she can make an informed recommendation about the timing of radiation. These are the kind of symptoms that my wife's oncologist wanted us to report even before the next scheduled appointment.
Good luck.
JimC
Forum moderator
Reply # - October 30, 2014, 08:06 PM
It isn't normal to have a
It isn't normal to have a major discrepancy between symptoms and imaging results. As Jim suggested, it's very appropriate to seek a consultation promptly when symptoms are worsening, rather than waiting a potentially long time.
I think it's important to seek palliative radiation if there is evidence of progressing, symptomatic bone metastases. The downside is that there would likely be a "washout period of a couple of weeks between completion of radiation and timing of start of treatment with a protocol-based treatment.
Good luck.
-Dr. West
Reply # - October 31, 2014, 06:16 AM
Hello Jim and Dr. West,
Hello Jim and Dr. West,
Thank you very much for both your replies. I spoke to the research nurse yesterday and she mentioned that we can certainly pursue radiation but as Dr. West had mentioned this might delay her from receiving the CO-1686 agent in the event the mutation comes back positive. It seems that the research nurse is leaning more towards having my mom wait until the end of next month to start receiving the CO-1686 agent before considering radiation. Having said that, the nurse also mentioned that radiation would only be done in the event to reduce her pain and not to prevent any complications from spine mets such as compression fracture etc.
We have an appointment next Thursday for the biopsy and another appointment tentatively set for the next day on Friday to see her medical oncologist at this research facility to discuss my mom's new symptoms. I was just wondering, given the timelines and my mom's new symptoms, do you think we should press for radiation to be done after the biopsy but before the results for the mutation comes back? We were told yesterday that it may take a minimum of 2 weeks, but realistically longer for results to come back because of processing time at this hospital prior to mailing out the sample to the US, which would bring us to late November, early December before systematic therapy can be initiated.
Also, she is currently on Alendronate/Vitamin D3 70mg/2800IU once weekly for her osteoporosis since 2010 prior to being diagnosed with stage IV lung cancer. I was just wondering if it would be worth asking for her to be switched to Zoledronic Acid injection (which I believe can be done once yearly) instead in hopes to further stabilize her spine and prophylactically prevent problems like spinal compression fracture, which as Jim has mentioned might cause irreversible damage? Again, many thanks for your valued input and looking forward to hearing back from you.
Best regards,
Will
Reply # - October 31, 2014, 07:43 AM
Hi Will,
Hi Will,
I don't quite understand what the research nurse meant when she said radiation would be used to reduce pain, but not to prevent problems such as fractures. The only interpretation that makes sense to me is that if your mom was not experiencing pain they would not radiate the lesions in an effort to prevent fractures. But she knows that your mom already has troublesome pain, so the point is probably moot.
Regarding Zometa (zoledronic acid), Dr. West has had this to say:
"Bone lesions can be associated with a higher risk for a pathologic fracture, especially if they're in a weight-bearing bone. With regard to your question of Fosamax and Zometa, these agents are in the same family, so you wouldn't give both. Zometa is better studied as a treatment to reduce subsequent progression of bone metastases, so it would be reasonable to consider transitioning from Fosamax to Zometa, but they haven't been compared in any meaningful way." - http://cancergrace.org/forums/index.php?topic=4710.msg47716#msg47716
Zometa is given once each year to prevent osteoporosis, but for bone met pain it can be given more often, as stated in the prescribing information:
"4 mg as a single-use intravenous infusion over no less than 15 minutes every 3-4 weeks for patients with creatinine clearance of greater than 60 mL/min." - http://www.pharma.us.novartis.com/product/pi/pdf/Zometa.pdf
[continued]
Reply # - October 31, 2014, 07:46 AM
[continued]
[continued]
There is a newer bisphosphonate available, but it is much more expensive than Zometa and may not be covered by insurance, as Dr. West explains:
"Zometa was found to be very slightly less active than XGEVA (denosumab) in preventing skeletal complications but is far more expensive, and either would be considered a very appropriate choice for someone with bone metastases from another solid tumor. XGEVA has the advantage of being a subcutaneous injection (under the skin), but again, since XGEVA is far more expensive and not significantly better in most ways, some insurers will cover Zometa but not XGEVA unless a person can’t tolerate Zometa." - http://cancergrace.org/topic/zometa-and-breast-cancer-bone-mets#post-12…
I hope you can have a good discussion with your mom's oncologist about the timing of radiation with respect to starting the trial drug.
JimC
Forum moderator
Reply # - October 31, 2014, 12:19 PM
Zometa should be readily
Zometa should be readily approved by an insurer for someone with lung cancer metastatic to bone. The issue, however, is whether it's better than alendronate, and I would not presume that to be the case. Zometa just happens to have been tested in this setting, while alendronate hasn't, but I suspect that they have very similar activity.
As a rule, we really can't answer questions about whether a patient should lobby for a change in the treatment plan proposed by their own physician, who clearly knows more about their case than we would. That would include a question of whether someone should push for radiation if that hasn't been recommended, or for Zometa instead of a similar agent.
I'm sorry we can't be more helpful here.
-Dr. West
Reply # - October 31, 2014, 01:21 PM
Hello Jim and Dr. West,
Hello Jim and Dr. West,
Thank you for your replies. I am also looking forward to discussing treatment options with my mom's oncologist next week regarding mets to bone. Of course I understand that this website can not make specific recommendations to treatment options, as this can only be done by the health care provider who is actively treating the patient. However, the added knowledge and ideas gained from this forum is invaluable and provides general knowledge that can be used to make informed decisions around treatment, of course after discussing these options with the treating physician.
Dr. West, after reading your reply, I take it that it is not worth changing treatment of bisphosphonate, but I will still consult the oncologist next week. If there is anything else you recommend or think would be a good point to discuss with the oncologist next week please do not hesitate to let me know. Again, much gratitude for all your help!
Best regards,
Will
Reply # - November 7, 2014, 10:05 PM
Dear Dr. West and Jim,
Dear Dr. West and Jim,
Just to provide a little update followed by a question. As per my post last week, my mom was experiencing gradual increasing in pain and symptoms for the past 2-3 weeks starting mid-October. However, just this week (i.e., past few days) my mom has actually been feeling better in terms of less pain in the thoracic spine area, and requiring less or no tylenol (albeit some pain remains). Having said that the most recent CT scan done 2 weeks ago reported overall little change in lung, however, there was an "interval development of a moderate pathological fracture of the vertebral body of T1".
We met with the medical oncologist today who suspected that the culprit of the pain is from the "hairline" fracture at T1. Since this fracture is not suspected to put her at risk for a subsequent catastrophic fracture (i.e., fracture that would displace the vertebral and cause damage to the spinal cord), and also since my mom's pain symptoms are improving, the plan is to wait for the next couple weeks until mutation test results come back before proceeding with a course of action.
In terms of bone medication, the oncologist favors Xgeva but worries it may be considered an anti-cancer agent (as opposed to one for osteoporosis) and therefore put my mom's chance of entering this trial for CO-1686 at jeopardy due to inclusion/exclusion criteria set out by the research company. Hence, she will continue with alendronate until biopsy results return until course of action for bone medication is taken also.
Here's my question:
1) My mom is on several naturopathic supplements, including: curcumin (300mg x2), fish oil (10mL), melatonin, and vitamin D. For 5 days prior to her biopsy (which was done on Thursday Nov 6), she did not take the curcumin and fish oil because of its potential to cause increased bleeding from biopsy. Do you think there is any good reason to suspect that my mom is feeling better now in the past few days because she was off the Curcumin and...
Reply # - November 7, 2014, 10:17 PM
(continued)... Fish oil?
(continued)... Fish oil? Could the curcumin and fish oil be somehow negatively interacting with the Iressa she was on, potentially mitigating Iressa's anti-cancer effects, which would explain why being off those 2 agents allowed Iressa to work and help reduce the pain? Or do you think the reduction in pain is likely because of fracture healing? The side effects of rashes on her scalp seem to have disappeared completely for the past 2-3 weeks when her pain increased, and now some scalp rash is starting to appear which seem to be associated with better symptomatic report of pain at the present...I'm just wondering if there is any remote chance the supplements are doing more harm than good and if she should consider stop taking them? (Keeping in mind she has taken them concurrently with Iressa ever since last year when she started taking Iressa and have been tolerating it well).
I was thinking, she could continue taking the curcumin and fish oil and see how her symptoms change; if it worsens then go off these 2 agents again and re-evaluate? Or do you think its worth remaining off these supplments completely?
I apologize for the long winded question. Looking forward to hearing back from you.
Best regards,
Will
Reply # - November 8, 2014, 06:16 PM
Will,
Will,
I'm glad she's feeling better.
Neither I nor, I believe, anybody else really has any idea of the potential interactions of these supplements with Iressa -- they haven't been studied. I have exactly no enthusiasm for supplements that have no actual clinical evidence to support their use, precisely because we don't know if these will help, hurt, or make no difference at all.
There are too many variables involved for me to blindly guess what might be the cause for her recent change in symptoms.
-Dr. West
-
Reply # - November 8, 2014, 06:16 PM
Will,
Will,
I'm glad she's feeling better.
Neither I nor, I believe, anybody else really has any idea of the potential interactions of these supplements with Iressa -- they haven't been studied. I have exactly no enthusiasm for supplements that have no actual clinical evidence to support their use, precisely because we don't know if these will help, hurt, or make no difference at all.
There are too many variables involved for me to blindly guess what might be the cause for her recent change in symptoms.
-Dr. West
-
Reply # - November 9, 2014, 06:55 AM
Hello Dr. West,
Hello Dr. West,
Thank you for your reply. I was thinking you might have this opinion towards supplements, which is very reasonable given the lack of evidence to support their purported use in this population. Having said that, hypothetically speaking if you had a patient who presented similarly as my mother in your practice, would you advise her to stop taking the supplements and monitor, continue/resume taking supplements and monitor, or some other course of action? Also, from your clinical experience, have you seen patients who seem to have been gradually worsening in terms of symptoms then make a comeback and improve spontaneously without any alternation in treatment course? Is there a possibility that Iressa may have somehow reduced it's efficacy, only to later on become re-sensitized spontaneously later on (that you have seen in your practice or know about)? Looking forward to hearing back from you.
Best regards,
Will
Reply # - November 9, 2014, 08:24 AM
Hi Will,
Hi Will,
As you know, the doctors here can't give advice about what a person who is not their patient should do. I understand that you are looking for guidance, but asking Dr. West to advise a "hypothetical patient" in your mom's situation is really just restating the request for advice.
As you can see from his previous comments, Dr. West does not favor supplements without proven value and whose possible interactions aren't known.
Generally cancer symptoms only get worse over time, and drug effectiveness doesn't tend to wax and wane, but Dr. West often states that "cancer can do anything" because just about anything has happened in his practice.
I hope your mom continues to feel better.
JimC
Forum moderator
Reply # - November 9, 2014, 12:33 PM
I appreciate Jim's protective
I appreciate Jim's protective stance (he's a lawyer, after all), and he's right that I can't provide medical advice to people here, even couched as a "hypothetical patient". Honestly, I don't have a stock approach for situations that aren't stock situations. I manage my patients in these situations in an individualized manner.
-Dr. West
Reply # - November 9, 2014, 01:05 PM
Hello Jim and Dr. West,
Hello Jim and Dr. West,
Thank you for your replies. Dr. West, I apologize for putting you in a difficult situation. This was actually a question I intended to ask the medical oncologist on Friday but seem to have gotten lost in the mix of other discussions we had that day. However, as you have mentioned his advice would probably be from clinical judgement rather than empirical evidence as studies are probably non-existent in this situation. Again your advice and kind words are much appreciated and I will keep you both updated.
Best regards,
Will
Reply # - November 17, 2014, 11:54 AM
Dear Jim and Dr. West,
Dear Jim and Dr. West,
Just to provide a little update. So after about a week and a half we heard back from the hospital today saying that the biopsy done could not be used for mutation testing because not enough malignant cells were found in the sample taken (there were about 5 samples taken). We are to see the medical oncologist (lead investigator of trial) regarding possible options moving forward from here on Wednesday (2 days from now).
The research nurse mentioned that there would be discussions on Wednesday around possible re-biopsy, or wait and see, or something else. I was just wondering what your thoughts are in this situation. Is there anything we should consider asking the oncologist during this visit to help us decide what the best course of action are in this situation? Do you think it would be wise to wait and see, re-scan a few weeks later and see if any objective changes are seen, which would help to monitor Iressa's continued effectiveness, as well as see if any new tumor grows that could be possible sites for a future re-biopsy? It appears that my mom's tumor is relatively small (millimeters) but numerous within both lungs and mets to spine. Since the previous biopsy was only done on the chest wall and not the lung itself, would be be wise to ask the oncologist to consider biopsy of the lung this time around instead? Subjectively, she is doing fine. She has no more pain and seems to be in good spirits. Looking forward to hearing your thoughts on this matter.
Best regards,
Will
Reply # - November 17, 2014, 01:31 PM
Hi Will,
Hi Will,
I'm glad to hear your mom is feeling better. After reading over the thread I wonder if she began taking the codeine cough medicine. If so it could be the source of pain relief as well. As for waiting, feeling fine can be used as an indicator for staying the course of iressa and waiting for rescan to make changes. When the time comes a rebiopsy may be an option and a rescan will help the pathologist make a decision on the best place to access tissue. And as always these decisions depend on the individual for whom only those involved in her treatment are the best to help with those final decisions. I've heard more than once a doctor state that there are as many different types of cancer as there are people with cancer.
All best,
Janine
Reply # - November 17, 2014, 01:48 PM
Hello Janine,
Hello Janine,
Thanks a lot for the reply. Actually my mom is currently not taking any pain medication as her pain seem to have resolved almost completely. Besides the extra-strength teylenol which she had to take starting Mid-October for about 3 weeks, she did not need to switch to using codeine. Again, I wonder if this is because of the T1 compression fracture that was the culprit of the pain, and now that inflammation has resolved in this area, so has the pain and discomfort she was experiencing.
In any event, I'm thinking it might be wise to consider continued treatment with Iressa and re-scans done a short time afterwards to see if she is still responding well to Iressa or if another treatment is indicated - if so, whether it be re-biopsy to try the CO-1686 or chemo to stop progression. I'm also wondering if the CT scans taken during the CT-guided biopsy is available and can be used to guide making decisions about when to re-scan and if progression was seen. Those are just my thoughts but again I am not an expert by any means so I thought I'd collect some insight here prior to the meeting Wednesday with the oncologist before a decision would need to be made.
Best regards,
Will
Reply # - November 17, 2014, 07:30 PM
Will,
Will,
I hate to be unhelpful, but the way I see it, these questions are all ones that require careful judgment that includes reviewing the films to see the pace of change and extent of cancer, seeing directly how your mother is doing clinically, and reviewing all of the options. This is what you're getting with an expert opinion, so rather than go in with a plan half-baked based on incomplete information, why not learn what the consultant recommends and then review the merits of that proposal, or array of options?
-Dr. West
Reply # - November 17, 2014, 09:31 PM
Dear Dr. West,
Dear Dr. West,
Thank you for your honest opinion. You may think that your response is unhelpful but in fact knowing your thought process on the matter is very valuable and much appreciated! For example, knowing to consider rate of change based on film analysis is something I may not have considered but now will keep in mind when discussing options with the oncologist on Wednesday. I just wanted to garner as many ideas as possible to help enhance the breadth of the discussion and not leave any stones unturned sort of speak, during this important meeting. I guess in a way I was trying to obtain a second opinion, before receiving an official opinion from the treating oncologist, in order to help add further confidence in our decision on what to do next, whatever that decision may be. Again, many thanks for taking the time to read through and in answering my questions. I will try to keep you updated.
Best regards,
Will
Reply # - December 19, 2014, 08:08 AM
Hello Dr. West,
Hello Dr. West,
Hope you are doing well and enjoying the holiday season. I just wanted to provide you with an update and ask a question.
Approximately 4 weeks ago we were seen by my mom's research oncologist regarding the results of the biopsy. It came back inconclusive because the spot that was chosen for biopsy (the left pleura) was unfortunately the spot that had a pleurodesis done about a year and a half ago, which resulted in lots of scarring found in the biopsy and not enough malignant cells to be analyzed for mutation.
The plan that was proposed was to wait and see. So my mom is having a follow up in early January, with CT scan and Bone scan to see if there is any more spots that are bulky that can be biopsied for consideration into the trial. She has multiple supraclavicular lympth nodes that are palpable (at least 3 that can be felt) on the left side, and my mom's oncologist thinks that is a reasonable spot to look into for biopsy, although the research oncologist last month mentioned that it could be inflammatory and may result in another inconclusive biopsy. The plan is to wait and see how January's CT scans go and if there is a spot worth biopsying they will try for it. If there isn't and the bone continues to progress, perhaps focal radiotherapy to the bones and continue with Iressa will be implemented. If there is disperse spread, then perhaps chemotherapy can be discussed although it seems that they are shying away from chemotherapy as a last resort. Currently, it seems like my moms back pain has subsided and she is not very symptomatic besides the on/off coughing that won't go away completely.
My question is:
1) do you think the lymph node at the neck is a viable option for biopsy
2) my mom had a lot of pain on the upper right quadrant of her stomach last night that lasted for about an hour, then it went away and she fell asleep. Do think
Reply # - December 19, 2014, 08:12 AM
...Do you think my mom should
...Do you think my mom should follow up with her oncology team about this or should she just wait and see how things go and wait for the CT scan in 3 weeks? I read pain to this area could be from mets to the liver. If this is the case, is there any merit to seeking follow up now or is waiting for another 3-4 weeks is okay. I.e., if there is mets to liver what can really be done medically?
3) What are your thoughts on the overall plan?
Thank you and looking forward to hearing back from you.
Best regards,
Will
Reply # - December 19, 2014, 06:00 PM
Hi Will,
Hi Will,
I think the question of whether the lymph node is a good target for biopsy is probably best judged by those on her medical team who are reviewing the films.
As far as the pain your mom experienced, if it was just one episode which has not been repeated, that would not be typical of cancer pain, which tends to occur regularly and worsen over time. On the other hand, there is never a problem with reporting new symptoms to her medical team. If the pain does come back, I would not hesitate to report it.
Regarding the plan to wait and see what appears after the scans, that certainly seems reasonable if there are no viable biopsy targets at present.
Best of luck with the next set of scans.
JimC
Forum moderator
Reply # - December 19, 2014, 06:43 PM
I would say that it is very
I would say that it is very reasonable to try a biopsy of a lymph node that you can feel above the collarbone/clavicle, but the probability that they are cancer vs. inflammatory is a function of the size of the nodes -- if just 1-1.5 cm, they could be anything, but if these are getting to be 2-3 cm or larger in diameter, and especially if they get that big and are very firm, that is likely to represent cancer. At the same time, there aren't many places to biopsy that are easier to get to than a palpable lymph node, so if it doesn't provide a conclusive answer, you haven't lost anything.
As Jim noted, having a one-time pain that spontaneously improves or resolves isn't very characteristic of cancer. A new symptom that shows an escalating pattern is of far greater concern than a seemingly one-time event that goes away and doesn't repeat.
Good luck.
-Dr. West
Reply # - December 20, 2014, 11:37 AM
Hello Jim and Dr. West,
Hello Jim and Dr. West,
Thank you very much for your replies. It is reassuring to read from you that my mom's one-time episode of pain is not characteristic of cancer and I am hoping that it doesn't recur and become problematic - if so, I'll report it to the oncology team as advised. Also, the information on the lymph node size in differentiating inflammatory vs cancer is very helpful. I hope everyone has a great holiday and we'll touch bases soon after the next set of scans.
Best regards,
Will
Reply # - January 4, 2015, 11:12 PM
Hello Dr. West and Jim,
Hello Dr. West and Jim,
Hope your holidays have been pleasant and you are enjoying 2015! I just wanted to give you and update and ask a few follow up questions.
Since Christmas my mom started to experience recurrence of her thoracic pain, which required some tylenol extra strength. In the next few days she had on and off pain, and on December 28th, she had a lot of pain on both her lower thoracic/rib area. She also experienced a lot of pain and difficulty transferring in and out of bed/couch, coughing seems to make it worse, etc. I suspected that she had experienced another episode of spinal compression fracture and/or new fracture of her ribs (she had a T1 fracture back in October, but she only experienced pain 2-3 weeks then it spontaneously went away). I called her hospital to get the dates of her scans moved up 1 week to the last week of December.
Last Tuesday she had a CT scan done of her chest/ab/pelvis and head/neck. Tomorrow she is having a bone scan done, and Wednesday we are back at the research oncologist's office to discuss scan results and possible options for biopsy for considering into the trial, radiation and continued Iressa, or chemo if it comes to it.
My questions are:
1. She has been taking diphenylhydrdamine 25mg tablets to help her sleep through the night for the past few weeks-1month (self prescribed). I'm just curious if you have any knowledge of this over the counter allergy medication and its possible interaction with Iressa or her cancer treatment? I'd like to think that the new symptoms are not contributed from taking this new medication and there isn't harm in taking it long term for patients with lung cancer in her situation.
2. Although she has been taking alendronate 70mg for osteoporosis, she seems to still be progressing in her bones. Do you think its again worth bringing up the option of switching to Xgeva with her trial oncologist in hopes of slowing down the progression? I'm thinking radiation might be an option.
Reply # - January 4, 2015, 11:19 PM
3. she has been bracing her
3. she has been bracing her thoracic-lumbar spine through an over the counter circumferential lumbar support brace, which seems to be helping. Just wondering what the typical options are for patients with bone mets and fractures. Could the brace actually be doing more harm than good despite her feeling better with it on? e.g., displacing the bones more through the compression of the brace for example in the case of a rib fracture? I'm guessing pain would be a good guidance. I'm just curious because she will probably keep the brace on until we see her oncologist to discuss the results on Wednesday so just wondering if you think its safe to keep it on or should she wait to see the results of the scan and possibly be prescribed a more custom brace at that time. What are typical treatment options in this case? I read vertebroplasty might be an option.
I apologize for the long read in advance and thank you for your efforts in replying. Looking forward to hearing back from you.
Best regards,
Will
Reply # - January 5, 2015, 04:27 AM
Hi Will,
Hi Will,
I don't see any interactions listed between Benadryl (diphenhydramine) and Iressa, but as a general rule it's usually a good idea to discuss the use of any over the counter medications with your oncologist.
As Dr. West discussed earlier in this thread, Xgeva has been shown to be somewhat more effective than Zometa, which he compared in effectiveness to alendronate (Fosamax). It's certainly worth discussing with your oncologist, and an option if your insurer will pay for Xgeva. But you are correct that if possible, radiation tends to be the best treatment for progressing, painful bone metastases.
Although as you say pain tends to be a pretty good indication of whether a solution such as a brace is causing harm, your question about the brace she's using is one that is best left to her own medical team, including at some point an orthopedist.
Good luck with your meeting on Wednesday, and please keep us up to date with the results and any questions you may have.
JimC
Forum moderator
Reply # - January 5, 2015, 10:19 PM
To my knowledge, Jim is
To my knowledge, Jim is exactly right.
I don't know of any negative interaction between benadryl and any EGFR inhibitors.
The evidence is clearly stronger for XGEVA (denosumab) than for alendronate, and the decision to have her on alendronate rather than XGEVA isn't one based on evidence. I wouldn't presume that XGEVA will be significantly superior or that it will make any material difference, but the evidence is stronger for it.
I wouldn't want to speculate about the safety of a brace and the mechanical effect on possibly metastases. We typically favor radiation for treating pain and risk of a pathologic fracture (fracture from metastasis-related structural instability of a bone)...otherwise, surgery is rarely pursued as an alternative.
Good luck.
-Dr. West
Reply # - January 6, 2015, 11:18 AM
Hello Jim and Dr. West,
Hello Jim and Dr. West,
Thank you for your replies. We will discuss these options with my mom's oncologist and hope for the best in terms of results of the scans and next steps. I'll keep you updated on the progress.
Best regards,
Will
Reply # - January 7, 2015, 09:08 PM
Hello Dr. West and Jim,
Hello Dr. West and Jim,
So we just got back from the appointment with the oncologist and here is a brief summary. There is multifocal disease progression of bilateral lung, progressive pleural nodules, increase in axillary lymph node metastases, progressive bone mets, with a new pathological compression fracture at T8 vertebrae.
The good news is that there is no new mets to brain, abdomen or pelvic areas. It seems as though overall there is slight interval progression, but again nothing in the lung that is bulky enough for a biopsy. Having said that there is a 1.9 cm enlarged supraclavicular lymph node that is a potential place to have biopsy done.
So here is the plan:
- get a biopsy of the enlarged supraclavicular lymph node via US guided and try for T790M mutation testing again
- referral to radiation for new spine mets that is causing pain now
- oxycodone for pain as needed prescribed
- Xgeva prescribed
Here are my questions:
1) I read from other patients who are on Xgeva that they were also prescribed supplemental Vitamin D and Calcium pills. Is this commonly used along with Xgeva or would my mom need a blood test to determine her current levels and determine necessity and dosage? The onc actually just gave us the prescription to fill but we weren't privy to this piece of information at the time. (Mom's on 4000 IU vitamin D supplments daily, no calcium so not sure how this plays into the decision).
2) Do you know if alendronate is generally stopped when someone is using Xgeva or do they continue on with both? I'm thinking we should stop alendronate but not 100% sure, I can always call to ask.
Reply # - January 7, 2015, 09:12 PM
3) Besides the CO-1686 and
3) Besides the CO-1686 and AZD9291 trial options, we were also given the option of an apparently new trial that just opened up in North America in Phase II, i.e., the EGF816 by Novartis. This was the first time I ever heard of this agent so I was wondering if you had any experience with it and if you could possibly comment on the level of evidence for this agent in comparison to what has been reported for the other 2 agents that seem to have break through status.
Again, thanks a lot for all your help and looking forward to your replies!
Best regards,
Will