Poorly differentiated Pulmonary Adenocarcinoma – Stage IV

Portal Forums Lung/Thoracic Cancer ALK Inhibitors Poorly differentiated Pulmonary Adenocarcinoma – Stage IV

This topic contains 119 replies, has 6 voices, and was last updated by  DJ Nikkam 4 months ago.

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April 15, 2016 at 10:24 am  #1273611    

Craig

I don’t know the answer for you but I do know that many patients who do well on crizotinib notice an improvement in symptoms within days and I’ve also known (online) patients who continued to have pleural effusion production while otherwise getting a good benefit.

Speaking as a fellow patient, if I were in your shoes and continuing to feel cancer symptoms, though, I would be impatient with my oncologist and seek CT or PET scan proof of benefit or not a little sooner than whatever normal is, or a re-test using FISH or gene sequencing, just in case it turns out that (1) your particular test result was a false-positive error or (2) the particular variant of your ALK driving mutation is one that requires a newer drug.

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib) for ROS1 trial @ MGH, Boston (5 yrs)
– carboplatin + pemetrexed (7 mo)
– TPX-0005 for ROS1 trial @ MGH (starting June 2017)

April 15, 2016 at 7:16 pm  #1273612    

DJ Nikkam

Dear Craig – thanks for your response. I am considering a retest using the FISH framework. My mother currently lives in India, and the ALK mutation “Test was performed using the Ventana anti-ALK (D5F3) antibody (CE-IVD) on the Ventana Benchmark XT automated IHC stainer”. Not sure if this is the same as FISH. Will check with her Oncologist.

I also read a few articles by Dr. Shaw. Very insightful particularly around the ALK re-arrangements.

Thanks
DJ

April 16, 2016 at 5:50 am  #1273617    

Craig

DJ — IHC tests are not FISH tests. I don’t know if my understanding of IHC is up to today’s technology but usually IHC is fast and cheap, and in recent years there have been some IHC tests that are about as good as the other two types (FISH and gene sequencing) when the resuslt says positive, but any test has a small risk of giving a false or misleading result. FISH potentially catches more unusual fusion partners involved in an ALK fusion rearrangement because it is just seeing if the two original halves of the gene have been moved apart rather than trying to find a specific pattern. Gene sequencing is the one that gives insight into which mutational variant of ALK is there and that can be useful if the one it finds is known to be resistant to one or more ALK inhibitor drugs you were trying or thinking of trying, but this is usually much more expensive and takes weeks and is usually best done on a biopsy sample of the portion of cancer that has been growing despite treatment.

FWIW, Dr. Shaw is my oncologist and she really is a “superdoc” in every way (including the lab team that makes her work possible) for ALK and ROS1. I’m very grateful for her and her work (as I should be). For ALK there is also superdoc Ross Camidge at U. of Colorado (incl. his team, e.g., Doebele) and he even has phone consultations available for $$$ not covered by insurance but may be cheaper than travel from far away.

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib) for ROS1 trial @ MGH, Boston (5 yrs)
– carboplatin + pemetrexed (7 mo)
– TPX-0005 for ROS1 trial @ MGH (starting June 2017)

April 17, 2016 at 6:24 pm  #1273637    

DJ Nikkam

Thanks much Craig. One follow on question::: how long before one get a CT or PET scan done (although the Onco seems to prefer CT), after starting on Crizo, to see how effective it is? Is it 4 to 6 weeks?

DJ

April 17, 2016 at 6:39 pm  #1273638    

Craig

That would be a doctor’s judgement choice under the circumstances there, I assume. If you are feeling nice improvement she/he might say anything from 6 weeks to 3 months, I would guess. If suspect the Rx isn’t working then maybe 6 weeks more or less. It can take time for CT to show measurable changes, but it exposes the patient to less radiation than PET and some prefer it (esp. in trials). PET might show you an early sign of reduced metabolic activity of the cancer before there is a measurable change to the dimensions of the cancer, but may be lower resolution — I get the impression PET is more often used to seek cancer that metasticized to other places they otherwise might not notice it, but let your oncologist explain her/his preferences and reasons. If your pesky problem is pleural effusion, I wonder if a simple way of testing might be to draw off some of the fluid and test it to see how many cancer cells are floating in it vs. the same test done before. Ask your on oncologist.

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib) for ROS1 trial @ MGH, Boston (5 yrs)
– carboplatin + pemetrexed (7 mo)
– TPX-0005 for ROS1 trial @ MGH (starting June 2017)

April 17, 2016 at 6:42 pm  #1273639    
JimC Forum Moderator
JimC Forum Moderator

Hi DJ,

Craig beat me to the “submit” button, but here’s what I wrote:

That’s a pretty typical interval. It’s long enough to show response, but not so long that you waste too much time on a treatment that is less than effective.

Many oncologists prefer CTs for follow-up.

As far as following progress with a CT vs PET, many oncologists prefer CT, and there is a GRACE FAQ on this subject here: http://cancergrace.org/cancer-101/2010/09/16/cancer-101-faq-assessment-response-of-cancer-to-treatment/

The conclusion is “Some people favor getting PET/CTs to clarify response in extreme detail, but there is a real risk of identifying clinically insignificant changes, such as by a minimal increase in the PET uptake of a tumor that remains stable in size, that might lead to a change in management that isn’t clearly necessary…Individual physicians have different perspectives about their reliance on PET scans and serum tumor markers in monitoring the course of a cancer, but for most solid tumors (cancers of solid organs where there is visible evidence of the cancer), changes in the size of known cancer on serial CT scans at regular intervals of follow-up remain the best studied and most validated way to assess response to treatment or monitor for progression off of treatment.”

Good luck with treatment.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

April 18, 2016 at 11:13 pm  #1273673    

DJ Nikkam

Dear Jim and Craig – you folks have been awesome in providing much need clarity and insights. Thank you so much for your time and inputs.

Dear Criag – as you have been on Crizo for a substantial duration, I was wondering if you could share your experience with how you dealt with fatigue… my mother is displaying interment severe fatigue with Crizotinib. She is on 250mg x 2, daily. Her other symptoms are Nausea and intermittent vomiting which is somewhat under control with Nausea medication. FYI – she started on Crizo on 4/7/16

Thanks much. DJ

April 19, 2016 at 2:07 am  #1273674    

DJ Nikkam

Also a follow on question – how long before Pleral Effusion (PE) subsides while on Crizo? My mom had her last PE drained on March 31 (they drained only about 800ml of the approx 2L that had accumulated). My mom has been on Crizo for almot 2 weeks now.. I am of the opinon that part of her fatigue could be also due to the remaining Pleural fluid in her lungs?

Thanks, DJ

April 19, 2016 at 4:50 am  #1273675    

Craig

Alas, I haven’t had fatigue on this drug. It did reduce my energy level due to, I assume, a combination of cutting my testosterone (severely) and lowering my BP & heart rate (about 10 points each). But it wasn’t bad enough to worry about and I just drink more coffee than I used to. I don’t recall if some patients are getting any kind of stimulants to try to compensate or not.

As to nausea, I want to remind you that many patients experience that and it usually stopped being a problem when they changed to taking their pills with food instead of on an empty stomach. When I started I was sure to take my morning pills after eating something to buffer them, e.g., shreadded wheat cereal was my preference, but a couple years later I experimented and found that I felt I was getting a little more benefit from the pills on an empty stomach and I didn’t have any nausea anyway, so I continued the practice of taking my morning pills on an empty stomach and trying not to eat solid food for a couple of hours, but I don’t recommend that to other people who do get nausea.

As to the pleural effusion, I’ll let the docs here give their experience across more patients. If I recall correctly comments & updates from my crizotinib peers, with some it stops building fluid immediately & the built up fluid gradually reduced over several weeks, but for others it persisted (despite having good cancer control elsewhere) and they eventually resorted to have a procedure done to relieve the symptoms. (I never had pleural effusion, but I did have bronchorrhea — fluid being produced in the lung airways, maybe an ounce a day, and it stopped [well, just a few drops] by my 2nd day on crizotinib.)

Best hopes,

Craig


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib) for ROS1 trial @ MGH, Boston (5 yrs)
– carboplatin + pemetrexed (7 mo)
– TPX-0005 for ROS1 trial @ MGH (starting June 2017)

April 19, 2016 at 6:40 am  #1273676    
JimC Forum Moderator
JimC Forum Moderator

Hi DJ,

With regard to the pleural effusion, I would just second what Craig has said. Response does vary quite a bit, and some patients who are responding well elsewhere in the body continue to struggle with such effusions. Two weeks is a pretty short time, so there’s still a very good chance your mom’s effusion will reduce. And you’re absolutely right that it could contribute to fatigue, since the extra pressure on the lung makes it work harder.

Hope it clears up soon!

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

April 19, 2016 at 9:31 am  #1273681    

DJ Nikkam

Dear Jim and Craig – thanks … my mom & I, met with her Onco today… given that she had extreme fatigue, shortness of breath, along with intermittent Nausea and Vomiting, I wanted her Doc to rule out Pneumonitis. He took an x-ray, and ruled out Pneumonitis.

He also indicated that the PE had subsided since the last x-ray on 3/31. Despite her PE having reduced, my mom is having significant dis-comfort, and shortness of breath. Her Doc will perform an Ultrasound tomorrow to determine the actual amount of fluid present in her left lung, and will most likely tap some of the fluid. Otherwise he indicated that the x-ray was clean (not sure what he meant exactly).

He further added that we wait for my mom to complete at-least 4-weeks on Crizo, before considering a CT scan…

I will also check with her Onco on when he would consider an MRI to ensure we pro-actively track any signs of Brain Mets… keeping fingers crossed.

Thanks
DJ

April 20, 2016 at 11:11 pm  #1273709    

DJ Nikkam

Dear Jim & Craig – an ultrasound scan revealed that there was around 1200ml of fluid in mom’s right lung. The doctor termed this as mild PE, and was of the opinion that we could wait it out.. however my mom continued to have severe fatigue and some sort of discomfort in her chest, that she decided to have the fluid tapped out. Around 700ml of the fluid was drained out. Also her blood reports indicated a normal liver function. Based on this the doctor has decided to continue with the current level of dosage (250mg x 2 daily). She continues to show significant fatigue and loss of appetite…any pointers will help

thanks much
DJ

April 21, 2016 at 4:39 am  #1273710    

Craig

Thanks for the update, DJ.

What did her oncologist say regarding the fatigue and loss of appetite and ways to deal with those?

For example, there are drugs (e.g., Megace) that can stimulate appetite if a person cannot afford to lose any more weight, but they come with significant side effect risks of their own.

As to the fatigue, I don’t recall there being a good answer to that. I have known fellow patients on one ALK inhibitor or another who have had very bad fatigue and resorted to lowering their dose and even skipping days often (which in once case seemed to mean insufficient inhibitor drug to keep the cancer under control). I thought I recalled some patients being offered some kind of Rx to try to help (e.g., a ADD drug, I think), but I’m not sure. I imagine a lower dose of crizotinib could help with the fatigue side effect but I wonder if it could be best to avoiding dropping to the 200mg instead of 250mg doses for at least the first couple of months (or even until the cancer reaches the most shrinkage it’ll get) — you could ask your oncologist about that and what effect that might have on duration of control. (BTW, 200mg might make sense for a small underweight person.)

If you want to find a lot of ALK patients some of whom have/had the same issues and may have mentioned (or could answer) what their oncologist had tried for them, try this discussion on another forum:

https://www.inspire.com/groups/american-lung-association-lung-cancer-survivors/discussion/anyone-on-pf-02341066-crizotinib-alk-gene-part-3/

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib) for ROS1 trial @ MGH, Boston (5 yrs)
– carboplatin + pemetrexed (7 mo)
– TPX-0005 for ROS1 trial @ MGH (starting June 2017)

April 21, 2016 at 8:15 am  #1273712    
JimC Forum Moderator
JimC Forum Moderator

Hi DJ,

It’s not clear from your post when the fluid was drained, but if it was just done a day or two ago, I wouldn’t assume that the full effect of doing so has become clear. An effusion of 1200 ml is large enough to cause shortness of breath and some fatigue, so draining over half of it may still prove effective in the days to come.

That will be my hope for your mother.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

April 21, 2016 at 6:01 pm  #1273719    

DJ Nikkam

Thank you for your responses Jim and Craig. Here is a brief chronology of events so far with regards to my mom’s treatment:::

– Mom – age 66 years.
– Had Total Knee Replacement TKR) of both legs during Sept 2015. Healed well.
– Initial Ca symptoms started Dec 2015 – persistent cough and severe fatigue
– Initially treated for cough, till Jan 2016
– Hospitalized for breathlessness on Feb 4, 2016. Determined via x-ray to have large PE in right lung
– First PE tapping to drain around 1.5L on Feb 5, 2016.
– Dx with Pulmonary Adenocarcinoma Stage-IV on Feb 15, 2016.
– First round of Chemo – Pemex + Carbo on Feb 25, 2016.
– Tested positive for ALK D5F3.(via Ventana anti-ALK D5F3 kit) on Feb 26, 2016
– Second round of Chemo – Pemex + Carbo on Mar 17, 2016.
– Another large PE (around 2L) seen via x-ray on Mar 31, 2016 (after second Chemo).
– Second PE tapping to drain around 850ml PE fluid on Apr 1, 2016.
– Onco decided to switch to Crizotinib – 250mg – twice a day starting Apr 7, 2016.
– Typical side effects on Crizo – Nausea, intermittent vomiting etc. Controlled via anti nausea meds
– Intermittent fatigue and loss of appetite. Increased fatigue and feeling of chest congestion – Apr 19, 2016
– Met with Onco on Apr 19.2016 X-ray indicated moderate PE. Onco ruled out Pneumonitis
– Ultrasound scan of lungs on Apr 20, 2016 showed around 1200ml of PE in right lung.
– Blood report on Apr 20, 2016, shows normal liver function. Dr decided to continue Crizo 250mg x 2 / day
– Third PE tapping to drain around 700mil of PE from right lung on Apr 20, 2016
– Significant fatigue and loss of appetite continues post PE drainage- Apr 21, 2016
– Mild fever (around 101deg) on Apr 21 / 22. Spoke to Onco, who prescribed paracetamol
– Follow up visit to Onco tentatively scheduled on Apr 22, 2016 to check on her fever / fatigue

Thought i will share this to provide a better context…

thanks
DJ

April 23, 2016 at 5:37 am  #1273735    

DJ Nikkam

Dear Jim & Craig – met with my mom’s Onco on 4/22. My mom had fever around 101, and was severely fatigued, loss of appetite, nausea and bloating caused by irregular bowel movements (more like constipation).

Her Onco got her admitted to address the fever, and stabilize her fatigue and other symptoms, and do a thorough evaluation. He also put a temporary stop on Crizo

Once my mom was stabilized via IV fluids + antibiotics for her fever, he performed a Contrast chest CT. While the CT scan indicated that the lesions had regressed (by around 25%), and lymph nodes were stable, her PE has increased. Her Onco felt the CT results were conflicting, as there was regression, and lymph nodes were stable, however there was an increase in PE. He was of the opinion that Crizo should have also controlled the PE

– For her PE, he was thinking that we should perhaps explore Plerodisis. This is on hold for now
– He had a follow discussion with the radiation oncologist today, who felt that there was regression with the exception of PE. However the radiation Onco left the overall decision to her primary Onco to make a decision on whether to continue on Crizo or consider an alternate
– For now her Onco has decided to restart my mom on Crizo once she stabilizes and her energy are up
– I have also requested an ALK-retest, using the FISH method (the initial ALK test was done via the Ventana ALK IHC test)

Fyi – my mom has been on Crizo for roughly 2 weeks (started on April 7). Prior to that she had two cycles of Chemo (Pemex + Carbo).

Will be great to hear your perspectives on this.

Thanks much
DJ

April 23, 2016 at 6:21 am  #1273736    

Craig

Given the apparent shrinkage outside the pleura, I’d expect an FISH ALK test would just confirm what you already know — it seems the cancer is either ALK+ (or is something similar that also responds to crizotinib). In this situation it might make more sense to consider a gene sequencing test of some kind to pinpoint the fusion partner (doesn’t make much difference) and detect whether there is any mutational variant emerging that is crizotinib resistant (which would justify a change to a different ALK drug). And I’d imagine your oncologist would want to only do that test on cancer that is growing and not on the cancer that is clearly shrinking. Right now the only growing cancer seems to be in the pleura and it is pretty easy to get a sample of the fluid, have a pathologist centrifuge it down to get a good sample of cancer cells, and test those. The odds are pretty good (not great, but good) that there will be enough cancer cells for this in the PE fluid and usually the cells found this way are mostly cancer cells. It is obviously one of the easiest biopsy approaches possible. What I don’t know is whether a gene sequencing test can be used on PE fluid samples (vs. needing something solid), but maybe they’d want to try the FISH test on that and/or run a panel of test to see if they can identify some mechanism of resistance — if none but a normal ALK fusion is found, then the problem might only be getting the crizotinib to penetrate into the interior of pleura well enough.

Plerodisis is very common for patients on crizotinib who continue to have problems with their pleural effusion (and not elsewhere). It does not always work, but if you ask them on discussion forums you’ll found that those it works for are quite happy they had it done. I’d recommend you ask them about their experiences with it, or just google and read their experiences.

(. . . continued . . .)


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib) for ROS1 trial @ MGH, Boston (5 yrs)
– carboplatin + pemetrexed (7 mo)
– TPX-0005 for ROS1 trial @ MGH (starting June 2017)

April 23, 2016 at 6:29 am  #1273737    

Craig

(. . . continuing . . . )

https://www.google.com/webhp?tab=gw&q=&gws_rd=ssl#q=pleurodesis+site://www.inspire.com/groups/american-lung-association-lung-cancer-survivors/discussion/anyone-on-pf-02341066-crizotinib-alk-gene-part-3/

As you may know, Alimta (pemetrexed) combined with a platinum-based chemo has pretty good odds for ALK patients (because they are usually never-smokers, not necessarily because of the ALK). If your oncologist felt it was working before the switch to crizotinib she/he might recommend trying to finish off that series of treatments later.

I still have no special thoughts about the fever & fatigue. If your oncologist felt the fever might be a reaction to the drug I’d recommend she/he contact an ALK expert like Alice Shaw (at MGH in Boston) or Ross Camidge (U. Colorado outside Denver) for her/his thoughts on how to manage use of the drug better. These 2 docs have probably seen & studied more ALK patients than anyone else (though others, like at Sloan Kettering in NYC or somewhere in China will eventually see more just because they serve more people). Most likely a reduced dose (200mg instead of 250mg doses 2x/day) will be tried, but the fever raises other questions I’m ignorant of.

Best hopes,

Craig in PA


- Stage IV never-smoker ROS1-driven m-BAC indolent adenocarcinoma
– Dr. Alice Shaw’s Xalkori (crizotinib) for ROS1 trial @ MGH, Boston (5 yrs)
– carboplatin + pemetrexed (7 mo)
– TPX-0005 for ROS1 trial @ MGH (starting June 2017)

April 23, 2016 at 7:32 am  #1273739    
JimC Forum Moderator
JimC Forum Moderator

Hi DJ,

Just to add a note to the excellent information Craig provided, it is possible to perform gene sequencing on cancer cells from a malignant pleural effusion (as was done from my wife’s pleural effusion eight years ago), and is a valid testing method as discussed in this paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841772/

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

May 4, 2016 at 8:32 am  #1273887    

DJ Nikkam

Dear Jim and Craig – thanks much for the detailed information. My mom is continuing on Crizotinib at the moment. Met with her Onco yesterday.. we did an US and it was determined that the PE in her right lung persists. Currently she has around 1000ml of fluid. It is around 3-weeks since she is on Crizo.. her symptoms seem under control, however PE is persisting. I did mention to the Doctor after running a gene sequence test on the Pleural fluid.. He is still undecided on this… My mom lives in India, and the process here moves somewhat slow.. Will let you all know how it goes

thanks / DJ

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