Any updates on treatment of bronchorrhea - 1249785

linnea
Posts:14

Dr. West, I have been trying to conduct online research about possible treatments to address bronchorrhea. I have mucinous BAC (ALK+) and although I am seven and 1/2 years out from diagnosis, bronchorrhea has been a troublesome side effect only recently. I have had more extensive disease at earlier dates, so it is a bit curious. However, I am slowly developing resistance to my current therapy (LDK378) and the worsening of the bronchorrhea does correlate. I do wonder if my lung tissue may also be less viable than previously (scarring?) and if this may be a contributing factor.

However, what I would really like to know is whether or not there have been any developments in managing this (unpleasant) symptom? The earlier evidence that Iressa was helpful, was that only in patients who were EGFR+? Is your thinking that the best management is still to address the underlying disease? It is a tough call for me, as I would like to stay on my current therapy as long as possible (for all the obvious reasons but also because there are few ill effects on my quality of life).

I know this is an area of interest for you and that it is an uncommon side effect of a less common form of BAC, so I am hoping you might have some insights to offer.

Thank you!

Linnea

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Reply # - November 1, 2012, 03:45 PM

double trouble
Posts: 573

Linnea,

It's nice to see you here on Grace. I enjoy your blog, and was particularly touched by your tribute to Stephanie.

I recently have been seeing a pulmonary physician who is very convinced that what is going on with me is a BAC, and he is working with me on controlling my very annoying symptoms. He has mentioned both bronchorrhea and bronchiectasis, and it seems that there is some infectious process going on. He prescribed a steroidal nasal spray and a macrolide. I still have symptoms of very viscous mucos that is hard to expectorate, but nowhere near to the degree that I had it. I just started this course, so we'll have to see how things go in the long term. I'm still constantly clearing my throat. I think you are a pretty informed patient, so perhaps you have already explored this route.

I am also ALK positive and will be starting Xalkori soon. A personal thanks to you for blazing the trail in clinical trials. Thank you also for mentioning LDK378... something new for me to learn about. It's good to keep the hope going that there are new therapies emerging that might help with the chronic management of this disease.

I look forward to your discussion with Dr. West.
Debra

Reply # - November 1, 2012, 04:00 PM

linnea
Posts: 14

Hi Debra; thanks for the warm welcome (and boy do I miss Stephanie). I wish you good luck on Xalkori.

Thanks for sharing your own experience. I do think there could be an infectious component to my symptoms as well, as they have subsided somewhat when I have been on antibiotics (not prescribed specifically for my symptoms, but rather for other obvious infections). Also, I should have mentioned that recently I have been using a nebulizer, which does help loosen secretions (but also prolongs the period of coughing and throat clearing at night).

Linnea

Reply # - November 1, 2012, 04:22 PM

double trouble
Posts: 573

Here's a link to a discussion I had with Dr. Walko that might interest you. Maybe something will jump out as worth trying. I wish you luck and hope you will keep us posted on what you decide to try. Dr. West has stated in the past that this is notoriously hard to manage.

http://cancergrace.org/topic/new-new-plan/page/6/

You might have to scroll down a bit to get to the part of the discussion that relates.

Good luck!
Debra

Reply # - November 1, 2012, 04:31 PM

Dr West
Posts: 4735

Linnea,

I'm sorry to say that I don't have any updates to offer. I do think that the efficacy of Iressa (gefitinib) or another EGFR inhibitor is likely to be through the more direct effect on the underlying cancer -- overall, I think that by far the most effective treatment avenue for the bronchorrhea is to suppress the underlying cancer. Honestly, I feel that all we really do otherwise is flail but not have any really meaningful impact on bronchorrhea. I certainly haven't found any gratifyingly effective treatment for it, though I wish I had more constructive things to suggest. It may be uncommon, but it's very troubling for the patients who experience it, and by extension frustrating for those of us who mostly just bite our lip wishing we had more useful strategies to manage it.

-Dr. West

Reply # - November 1, 2012, 04:53 PM

linnea
Posts: 14

Debra, I too have wondered about any commonalities between Cystic Fibrosis and mucinous BAC, but from my understanding CF presents with much stickier secretions (at least than I am experiencing) and obviously has a different underlying mechanism. Maybe someday there will be some crossover in treatment options though...I do believe that secondary infections can be a big problem in either disease...

Dr. West, thanks for your rapid and candid response. I am pleased that you clarified the relationship between Iressa and EGFR status--most of the information is so dated (and the cases isolated): it wasn't clear if the subjects were EGFR + or not.

I am disappointed yet not surprised that bronchorrhea is still poorly understood (at least from the treatment angle). As it happens, I had a discussion with my oncologist tonight. My scan from this past Monday shows continued subtle progression, but according to RECIST criteria, I am still experiencing response, so I have the option to stay on LDK for at least six more weeks. It comes down to deciding if the discomfort in the evening (primarily once I recline) is worse than any quality of life issues that may be part of what is likely my next treatment option (Alimta/carboplatin). As long as I can avoid infection, I think I will choose to put up with the bronchorrhea, while crossing my fingers that it will in fact subside once I start the next therapy.

Reply # - November 3, 2012, 07:33 AM

certain spring
Posts: 762

Best of luck, Linnea. I too have appreciated the stylish writing on your blog and your beautiful tribute to Stephanie.
I had one suggestion - physiotherapy, which I have found extremely helpful. I understand it is used in cystic fibrosis: more immediately, my uncle has advanced emphysema and it is one of the few interventions that works for him. I have a stent so a lot of mucus collects around it. The physio taught me simple postural drainage techniques that work well, as with the unfortunate sheep in Dr West's post. And massage helps too.
I'm a fellow nebulizer-user, and I've found that I have to try and let at least an hour elapse between the last session and going to bed, otherwise there is relentless coughing.
This is all on my mind because we are thinking about buying a bed with individual headrests, so that I can elevate my head and torso while my husband disappears under the pillows! Very best.

Reply # - November 3, 2012, 08:53 AM

linnea
Posts: 14

Certain Spring, hello and thank you :) My husband has wondered if some of the techniques employed for management of cystic fibrosis might be helpful, but he was thinking more along the lines of percussion of my chest--massage sounds much more pleasant! I will look into physiotherapy--I have already experimented with hanging my head over the side of the bed (after reading an earlier post by Dr. West in which he described a suspended sheep!). It is effective, but hasn't mitigated the coughing. I will try nebulizing earlier too.

Your night time scenarios are likely similar to ours (so romantic). I cough, hack and spit and my husband (who has now resorted to ear plugs) burrows. I often find myself apologizing, but so far he hasn't decamped to the guest room.

At one time (years ago) I actually had a hospital type bed, queen size with different controls for different sleepers. It was lovely, but bloody heavy and we were moving a lot so decided not to keep it. We now sleep on natural latex (I am also very allergic to dust mites, and it is hypoallergenic). Also very heavy (like a giant latex burrito--you have to roll it too move it) but quite comfy. We have propped the head of our bed up with risers, but I am getting to the point where I might need to invest in a wedge pillow (kind of hospital bed on a budget).

I really appreciate your insights, and I wish you the very best as well.

Linnea

Reply # - November 3, 2012, 09:20 AM

certain spring
Posts: 762

I can testify that the whole sheep thing is highly effective, if slightly embarrassing when people come into the room and find you lying on the floor (on side with cushion/pillow under hip), draining away. As to the percussive tapping, you need someone who understands what to do - people tend to thump me on the back, which is not helpful. A light drumming motion with the fingers is the right technique.
I am so glad to find someone who shares our night-time difficulties. My husband has been exceptionally tolerant but it can't be fun sleeping next to someone who sounds like a lizard learning to warble. I will suggest ear-plugs, that is a good thought.
My physiotherapist has actually been nagging me for two years to get a foam wedge to raise the pillow, so you're on the right track instinctively!

Reply # - December 2, 2012, 05:50 PM

linnea
Posts: 14

Dr. West (and others in on this conversation), I have been doing some more research on bronchorrhea and found this this excerpt from a recent publication (2/12) that references a case where gefitinib (Iressa) was used to good (and rapid) effect in a patient with bronchorrhea who was EGFR-

Here is the excerpt:

"Mucinous bronchioloalveolar carcinoma (BAC) can be associated with significant bronchorrhea. A 46-year-old man presented with BAC with 2,000 mL of sputum production on a daily basis, which prevented him from being extubated. As this condition is rare, there are only case reports outlining the therapy for the associated bronchorrhea. We used azithromycin, scopolamine, and inhaled fluticasone with moderate success. The initiation of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, resulted in dramatic improvement in the volume of pulmonary secretions produced. The patient's EGFR mutation status was subsequently found to be negative, which supports the hypothesis that the mechanism of reduction of bronchorrhea is independent of the antiproliferative effect of the drug."

And the link:

http://lungcancer.researchtoday.net/archive/9/2/7296.htm

My own situation has continued to become more challenging and I will be undergoing a biopsy on 12/12 and then starting chemo one week later (Alimta/carboplatin). I am very hopeful that my cancer shall respond to infusion and that the bronchorrhea shall begin to subside. However, obviously I remain interested in any news of a possible treatment for the bronchorrhea itself...your thoughts?

Linnea

Reply # - December 2, 2012, 07:13 PM

Dr West
Posts: 4735

I'm afraid I don't have any more information to offer today than I did a month ago.

I suspect that the conclusion that an EGFR tyrosine kinase inhibitor (TKI) like Iressa (gefitinib) working well in an EGFR mutation negative patient is independent of its anticancer effect is simply incorrect. We know that there can be heterogeneity in the tumor, so I think there's a very strong probability that most of the cancer that responded so well is EGFR mutation positive, even if the test said that the sample tested was negative. The authors might have also just tested for the most common mutations, but this person responding may have had a less common but still sensitizing variant of an EGFR mutation. Or the test itself might have been a false negative for some other reason. Either way, I would say that we see so much variability in testing outcomes and efficacy of EGFR TKIs that I wouldn't be at all inclined to use a single case to draw any firm conclusions about broader principles.

Good luck.

-Dr. West

Reply # - December 3, 2012, 12:52 AM

certain spring
Posts: 762

Hallo Linnea. I am sorry to hear of Events. However I have developed a great respect for Alimta - not on my own acccount but from people's experiences on GRACE. Best of luck with the combination, and hope it helps with the bronchrrhea.
I was thinking of you the other night - I have had a bad run where I have been keeping myself awake, or waking myself up, with the wheezing, whirring and whistling sounds. Very tiresome. Mercifully my husband has been away - some things are better experienced alone! All best.

Reply # - December 3, 2012, 07:43 AM

craig
Posts: 330

If I recall correctly
http://www.ncbi.nlm.nih.gov/pubmed/22277784
found phosphorylated EGFR (pEGFR) in all but one case of Xalkori-resistant ALK. So that makes me wonder if a 1st generation EGFR inhibitor (not a 3rd generation one that is more selective to mutant EGFR) might have some effect on the EGFR component of Xalkori-resistant ALK-driven lung cancer.

And it looks like
http://www.ncbi.nlm.nih.gov/pubmed/16009452
found EGFR TKI suppressed MUC5AC resulting in reduced mucin production in EGFR expressing cells. That lab analysis used A549 adenocarcinoma or NCI-H292 mucoepidermoid carcinoma cell lines as their model. I was not able to find any reference saying either of those cell lines had an EGFR mutation, so I assume they only express wild type EGFR; is that right?

I understand that a negative EGFR status can sometimes be misleading (e.g., formerly EGFR+ wiped out by chemo that remains responsive to EGFR TKI's as per http://jco.ascopubs.org/content/early/2012/07/23/JCO.2011.39.3744 ). So I suppose it is possible that something like that or even a false-negative result might have led to anomalous findings in the article Linnea cited ( http://lungcancer.researchtoday.net/archive/9/2/7296.htm ) which found EGFR TKI helped BAC bronchorrhea in BAC that was not found to have an EGFR mutation.

Of course, any single experiment or report could be subject to experimental or design error, exceptional result, or misunderstanding, but overall, considering the three citations together, is it plausible that an EGFR TKI might have a chance of reducing bronchorrhea in a EGFR-negative, pEGFR-positive ALK-driven Xalkori-resistant mBAC? If so, is the mechanism of action seen for Iressa (gefetinib) in the 2nd article likely to also apply to Tarceva (erlotinib)?

Best hopes,

Craig

Reply # - December 3, 2012, 11:09 AM

linnea
Posts: 14

Certain Spring, I am sorry that you continue to struggle with this troublesome symptom as well. It does leave one exhausted. Craig, I thank you for your comments and additional links. Catdander, I am not on this forum very often, but I confess to being confused by the implication that Craig's continued questioning is out of line. Craig also has mucinous BAC and has dealt with bronchorrhea too. It is an uncommon and poorly understood symptom and those of us who have been dealt this card are desperate to find any solution. Sometimes that means we do a lot of research on our own and pester both our own oncologists as well as any others who might have an opinion (Dr. West). I value Dr. West's input or I wouldn't take the time to post on this site, however I feel that there is no definitive answer to this question. There is simply not enough data to reach an iron clad conclusion. And even if there were, as someone who has been not only the exception to the rule, but the exception to the exception, I would still question it.

Linnea

Reply # - December 3, 2012, 11:52 AM

Dr West
Posts: 4735

I appreciate that. I think right now any promising anti-cancer therapy should be monitored for its potentially beneficial effects on bronchorrhea -- there's no question that it's very challenging to manage and that we don't know of any current therapies that are consistently helpful. I think the preclinical work can provide some speculative value, specifically to help prioritize what is most worth trying, but the only way we can really ever move beyond our current impasses is to actually see what these drugs do in real patients with bronchorrhea

-Dr. West

Reply # - December 3, 2012, 02:50 PM

catdander
Posts:

Oh dear, it seems I've been too vague. I'm very sorry I came across as suggesting you shouldn't be asking questions on Grace. It's what it's here for. I certainly would never have visited the site had I not had questions concerning my husband's cancer.

Let me try again.

Craig, you always impress me with your knowledge of your disease and your willingness and ability to share and broaden our knowledge. If I'm not mistaken Dr. Weiss has credited you with the idea of his lasted research.
As a moderator I help members find the answers to their questions. As you know many of the questions asked on Grace have been asked and answered many times over. In situations like that I find specific references and share them with new members. You and others do the same.

For many questions and I might suggest all the questions members such as Craig and linnea ask I contact a doctor, not Dr. West to give input. I thought you understood that so I was short with my comment about contacting a doctor. Again, sorry for the miscommunication.
As far as the whys for doing it this way, Grace is able to have more doctors giving input without having them need to scan the site for that opportunity. So for future reference you may give me a nudge and I'll make the contact. I read most of what's written on here.

Hope this explains some,
Janine

Reply # - December 3, 2012, 03:20 PM

linnea
Posts: 14

Janine, thanks for the explanation--email does have limits as a form of communication, and I appreciate the clarification and hope that I did not (again, the limitations!) come across as snippy. Persistent, I will cop to :)

Dr. West, I am glad you remain open minded toward the possibilities. I joked earlier with Craig that I feel as if he is my lab partner---as we have the same uncommon disease and different though possibly similar mutations (both have responded to crizotinib), I often benefit from his abilities as a both a diligent researcher and someone who can connect the dots with ease.

I for one remain intrigued by this possibility...in those places where Iressa can yet be prescribed, perhaps more opportunities to test this theory will present themselves.

Linnea

Reply # - December 3, 2012, 05:46 PM

craig
Posts: 330

Thank you for clarifying what you meant, cat. I misunderstood you at the time, but didn't worry about it for more than a second.

I doubt I should be credited for the idea of anyone's research project here (not yet), although I might have contributed some useful questions/references/thoughts that helped. But thank you for thinking that.

Best hopes,

Craig

Reply # - December 3, 2012, 10:19 PM

catdander
Posts:

Good luck to you both. I'm constantly impressed with those of you in the midst of cancer treatment and able to do so much of your own studying, deducing, and decision making.

Let me know if I can do anything to help.

Janine

Reply # - March 17, 2015, 12:37 PM

aunttootsie001
Posts: 324

Is there no simple answer as to how to subside this awful wheeze? I would sleep so much better with out it! I sleep with at least a 7 inch incline. It's hard to sleep higher because you slide down! Anyone find a solution would make me so happy! Lorrie!
As far as the Brain Rads I guess the Fatique is the worst I am having very much Rubber Legs! Lorrie

Reply # - March 26, 2015, 05:35 PM

aunttootsie001
Posts: 324

Well hi guys! Tomorrow will be on the count down! 4 more treatments! This Wholebrain Radiation has kicked my butt! I am finally noticing some hair falling out! In a couple weeks I'll be getting my hair cut off and I want to order a new cuter wig! Anyone have any idea's how long before side affects will subside. Would taking a vitamin help get me more energy? As you can tell I'm always full of Questions! Did I say food tastes like cardboard!

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