Poorly differentiated Pulmonary Adenocarcinoma - Stage IV - 1273125

Hi nikkam,

Welcome to GRACE. I am sorry to hear of your mother's diagnosis, but it's good to learn that her symptoms have improved and that she's tolerating treatment well. It's also great that she is ALK positive. As you know, that predicts a good response to ALK inhibitors such as Xalkori (crizotinib), which would usually be the choice for first-line therapy, but since she seems to be doing well with carbo/pemetrexed it makes sense to finish with that regimen.

You can search for trials at clinicaltrials.gov (even though it's U.S. based, it lists trials worldwide), although the current thought is to start with crizotinib and move on to a next-generation ALK inhibitor if acquired resistance develops.

JimC
Forum moderator

Hi DJ,

It's not uncommon at all to avoid the delays in molecular testing and begin chemotherapy, so the plan of action in your mother's case makes perfect sense.

There are some pretty good reasons not to add an oral ALK inhibitor while your mother is on chemo. First, it's not clear that there would be an increased benefit, and there is the possibility that the two could interact negatively, with one actually diminishing the effect of the other. Also, if only one of them is providing a benefit, it's impossible to know which one.

Also, as Dr. West has often said, treatment of stage IV lung cancer should be a marathon, not a sprint. So we seek to get the most benefit from each therapy used. That's one of the reasons to start with a first-generation ALK inhibitor (in your mother's case, after her chemo) then switch to a later-gen inhibitor when resistance develops; you get the full benefit of each.

And thank you for your kind words; despite the trouble I've been through, I feel extremely fortunate.

JimC
Forum moderator

Hi DJ,

Although there's no documented clinical trial evidence for it, in a previous discussion the suggestion was made that sucking or chewing on ice chips during the infusion may help prevent mouth sores, and GRACE faculty felt there might be a good reason that might work.. -http://cancergrace.org/forums/index.php?topic=3372.0

JimC
Forum moderator

Hi Nikkam,

Welcome to Grace. Following Jim's first response, oncologists tend to stay with a treatment that is working and not causing significant side effects. Particularly alimta for those who have the alk mutation seems to work very well. Also oncologists and their patients have a choice to continue alimta (or other non platinum based chemo) after 4 rounds of platinum doublet or take a break until 2nd line treatment is needed.

Continuing with alimta without a break after 1st line is called maintenance treatment. Taking a break after 1st line was standard up until 8 or so years ago. Maintenance treatment became a standard after trials suggested people did better with ongoing treatment. However many oncologist (even some who researched maintenance treatment) now believe that if that same patient is watched closely (reporting symptoms and getting regular scans) can do just as well with the break after 1st line.
Switching to crizotinib after first line treatment without a break is called switch maintenance and is used as well.
http://cancergrace.org/lung/tag/switch-maintenance/

Staying with alimta, changing to crizotinib, and taking a break are all reasonable choices. A lot depends on how the patient feels about it and how well the oncologist feels the patient will do with it. As a matter of fact a lot of treatment decisions moving forward will have that tagline, "it depends", which is why many people feel oncology is as much art as science.

I hope your mom does very well for a very long time,
Janine

I agree with Janine. If the CT scan shows a good response to Carbo/Alimta, then switching to maintenance Alimta seems to be ideal. She could potentially stay stable on the Alimta with good quality of life for years. It is nice to save the Xalkori pill in your back pocket, to start once there is a hint of tumor recurrence; otherwise you won't know if it is working or not. Our philosophy is to try to extend the benefit of each therapy for as long as possible, providing her quality of life is intact.

Hi DJ,

Although some oncologists like to use PET for follow-up, most oncologists prefer CT, which provides higher resolution images, even better than the CT portion of a combination PET/CT. That higher resolution provides the best comparisons in the size of tumors over time. PET, which shows hypermetabolic activity throughout the body, is good for staging, in order to highlight areas where there might be distant spread of cancer. That activity may represent inflammation or infection, but once cancer has been diagnosed, the best way to judge if progression has occurred, aside from clinical examination of the patient, is to look for growth in existing tumors, or the appearance of new nodules.

You may find this FAQ on methods of assessing response to therapy helpful.

JimC
Forum moderator

DJ,

New or worsening symptoms need to be addressed to her oncologist. It could be many things including more pleural effusion or tumor tissue breakdown but it's important to let her care team be aware in case of any immediate concerns.

I hope she does well,
Janine

Hi DJ,

I'm sorry your mom is feeling bad. Unfortunately as more cycles are given worsening fatigue is expected. If she is having trouble breathing it's important to call or see the doctor right away. Otherwise getting breathless from even just a little exertion maybe normal but that should be discussed with her care team to make sure.

Edema/swelling is a common side effect of chemo and likely not associated with SVC syndrome. SVC syndrome is only seen in about 3% of people with lung cancer. If it's decided (usually by CT) that she has it her oncologist may have her seen by a radiation oncologist.

It's pretty common not to see results from first line chemo until about 3 or 4cycles but your concerns are certainly something to be brought up in her next appointment.

I hope you mom is feeling alright otherwise.
All best,
Janine

Hi DJ,

Unfortunately everyone doesn't respond to our best chemo options.

It's not uncommon to have a pleural effusion that is loculated, meaning the fluid is suspended in separate pockets. For each pocket there would need to be catheter put in; each cath is invasive, painful to put in and runs the risk of pneumothorax. If this is the case it would make sense to drain just part of it, enough to feel better.

It's possible and believable the oncologist is afraid the PE will become worse if a change isn't made. A switch to crizotinib would be considered the primary choice for next line treatment for ALK rearrangements.

All best,
Janine

Hi DJ,

It is true that a change in the size of a pleural effusion is not a strong indicator of progression, especially if a follow-up CT indicates shrinkage in the size of the tumors. You can find a discussion of a similar situation (in which the follow-up scan showed improvement after treatment) here.In such a situation, a change of treatment is not thought imperative. Perhaps your mother's oncologist feels that, with an ALK rearrangement, there is a very good option available in crizotinib, but many oncologists prefer to get the maximum benefit from each line of therapy used. In that light, if the current chemo regimen is shrinking the tumors, an enlarging pleural effusion would not necessarily be seen as dictating a change of therapy.

JimC
Forum moderator

Hi DJ,

I certainly see his point of view that a worsening of cancer symptoms a week or so after 2nd cycle isn't a good indication that things are moving in the right direction. Since a first line platinum doublet should pack such a powerful punch you wouldn't expect her to get worsening cancer symptoms.

There just isn't a definite recipe for treatment in a case like this or most lung cancer settings and changing to crizotinib makes sense. Crizotinib can be extremely effective for months or even years and there is already a second generation option waiting in the wings.

From a patient's point of view a cancer center is a life support, however ask anyone who's gotten chemo in one and they will give you a dozen reasons why a pill taken at home is better than IV chemo taken at the cancer center. Plus side effects are usually much easier to deal with.

I think you could argue the scanning issue but it doesn't seem to be the battle that needs to be argued here.

I hope your mom does very well for a very long time.

Janine

Hi DJ,

I tend to agree with Janine. Even though it would certainly be reasonable to continue with two more cycles of the current regimen, since there is doubt about its efficacy, a change to a targeted therapy which provides a very good chance of success given the presence of the ALK rearrangement, switching to crizotinib is a quite reasonable choice. Much of the response to first line chemo is seen as a result of the first two cycles, and your mom has received those two rounds. And if there is real progression, switching now gets your mom started on a new treatment which, as Janine stated, hopefully will be effective for a long time.

Oncology is an art as well as a science, and there usually aren't right and wrong choices between reasonable alternatives.

JimC
Forum moderator

Hi nikkam,

It's true that with crizotinib, which has proved quite effective for patients whose cancer is driven by an ALK rearrangement, the first signs of progression are often in the brain. Most anti-cancer drugs have at least some difficulty penetrating the blood-brain barrier, although there has been a bit of evidence that Alimta may be a bit more effective. It is certainly possible that the chemo successfully prevented cancer cells from reaching the brain, but if cancer cells remain elsewhere, there is still the chance they will reach the brain.

JimC
Forum moderator

Hi DJ,

Although headaches can certainly be caused by brain mets, the mild, off and on type you describe aren't the kind that are typical. And if they are relieved by acetaminophen or other pain relievers, they're also not likely to have brain mets as their source. More severe headaches, focal weakness, double vision and seizures are symptoms to look for.

JimC
Forum moderator

Hi DJ,

This is a question many people taking crizotinib have. Studies show crizotinib has efficacy in the brain for some people but not as large a percentage as the 2nd generation of ALK inhibitors. Still some people certainly have efficacy in the brain with crizotinib. Unfortunately we don't know who those people are going to be.

The standard of care is to do an MRI of the brain at diagnosis then only if symptoms occur. However with more people able to control cancer in the rest of the body for longer periods of time the brain can become a sanctuary site for cancer.

Dr. Horn in her recent video stated she does MRI scans for those with known brain mets as often as she does chest scans. She didn't however suggest she would scan the brain for those without known brain mets. The link to this video is pasted below. The discussion details the stats for ALK inhibitors' efficacy in the brain. If you've not watched it it will certainly be helpful.
http://cancergrace.org/lung/2016/01/03/ar_2015_horn_blood_brain_barrier…

For an answer to your question I'll see if Craig can comment.

I hope your mom is doing better,
Janine

About half of Xalkori (crizotinib) patients see their progression as brain mets, as you'd imagine given only 0.3% of the blood level of the drug penetrates a healthy blood-brain barrier. Sometimes it works on existing brain mets in crizotinib-naïve patients, but that's a risky gamble when time is short.

As a patient on Xalkori (crizotinib) for 4.5 years, I am a fan of proactive periodic brain MRI's in most (not all) crizotinib patients. I think it's reasonable to push for scans at least every 6 months (or maybe every 6 after the 1st 10-12 months). Many patients get them every 4 months (great!) and some more often (e.g., if had brain mets before). In the past, it didn't matter given survival was only a year anyway, but new ALK drugs can give us years.

I'm a fan of scans because (1) early treatment of brain mets might enable potent targeted radiation rather than riskier WBR, and (2) I have read patients report "suddenly" having brain mets or lepto (even just 2 months after a prior brain scan) and (3) I have also known people whose brain mets or lepto (leptomeningeal carcinomatosis) excluded them from promising drug trials that could have extended their life. Trials of experimental ALK drugs that are already showing evidence of being able to penetrate the brain aren't as restrictive as they used to be, but there still may be a lepto exclusion sometimes.

On the other hand, in my case I have a mBAC-like adenocarcinoma (slow & not spreading outside the lungs), so the odds seem pretty low it'd spread to my brain or grow quickly between scans. So it makes sense that my onc scans me only annually (and I wonder if she'd order them at all if I weren't one of the first dozen crizotinib-for-ROS1 trial participants). Yet I knew an ALK+ patient diagnosed by biopsy with mBAC subtype adenocarcinoma whose cancer nonetheless spread to her brain proving "low odds" still means "it does sometimes happen." So I'm grateful to get scanned periodically.

Best hopes,

Craig in PA

P.S., Keep in mind that stage 4 patients with a very useful driving mutation seemed to have a 30% chance of surviving 5 or more years according to one source I read a couple years ago, a huge change from the 1-2% odds of several years prior. So it might be a change for your oncologist to have to think of how to avoid or mitigate dangers that might suddenly shorten the possibility of a 5+ year run to only months left.

Best hopes,

Craig in PA

One more thing. In another discussion elsewhere someone who had just visited ALK & ROS1 superdoc Alice Shaw said that in his case where crizotinib achieved NED (no [scannable] evidence of disease) she recommended CT scans every 3 months and brain MRI's every 6-9 months. Of course, you case can be much different. I'd assume that NED makes brain mets a little less likely, but not necessarily so, so I wonder if that's why she said 6-9 rather than 6 months or if there were other reasons? I don't know.

Hi DJ,

I'm sorry to hear of your mother's problem with nausea and vomiting. If she doesn’t already do so, taking an anti-nausea medication (such as Zofran) on a schedule, rather than waiting for nausea to develop first, can be very effective. It's harder to get rid of than it is to prevent. It may be that preventing the nausea and vomiting may help bring back her appetite. Also, eating small amounts of food frequently is better than larger portions, and you may need to experiment to find foods that are appealing (and you may need to think outside the box; a number of GRACErs have settled in on some pretty strange choices!) Don't worry so much about balanced nutrition at this point; getting in calories is important now. One of the fortified drinks such as Boost or Ensure may help.

My wife’s chemo nurse also suggested taking a walk to reduce nausea, and that did seem to help.

It’s also possible that her current anti-nausea medication just isn’t working well for her, so you may want to talk to her doctor about an alternative. Dr. Harman discusses various remedies for nausea here: http://cancergrace.org/cancer-treatments/files/2012/08/Dr.-Harman-Nause… and Dr. West discusses the use of acupuncture here: http://cancergrace.org/lung/2007/11/25/acupuncture-for-nv/

Good luck with solving that vexing problem.

JimC
Forum moderator

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

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

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

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-…

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

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

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