What We Learned: The Importance of First-Line Treatment

In my April 19 post, I tried explaining some things about my understanding of stage 4 cancer.  I should have started with a disclaimer – I am not a medical professional, and have no medical background.  When you read this, please don’t think of it as any more than some advice an untrained friend might give you.  I’ll probably get a few things wrong along the way, so you shouldn’t follow anything I say without discussing with your doctor.  Plus, every situation can be different, and what I know is specifically focused on metastatic gastro-esophageal cancer.

Ok, with that out of the way, I want to talk about something we learned about cancer treatments.   When it has been decided that chemotherapy is the best course of action, doctors will recommend a particular regimen of one or more chemo drugs.  For some cancers and conditions, there is a general consensus about what that regimen should be.  For stomach cancer, there is no such agreement among oncologists.  There are a handful of different primary drugs, plus numerous additional drugs that can be combined with one of the primary drugs, resulting in dozens of options.  Most oncologists will follow the National Comprehensive Cancer Network (NCCN) Guidelines, and the 2012 guidelines for metastatic gastric cancer listed 31 chemo regimens approved for first-line therapy.  

First-line therapy essentially means that you have not received any chemotherapy for this specific condition before.  Once you start a particular chemo regimen, you can stay on it for weeks, months, or years (or however long it continues to work for you while your doctors believe there is a reason to continue treatment).  No matter how long you stay on the chemo, as long as the drugs don’t change, that is considered first-line treatment.  Once you alter the chemo drugs and start a different regimen, that is considered the second-line of therapy.  If you altered them again, that would be the third-line, and so on.  Why would you change regimens?  The main reasons would be if the drugs stop working (your tumors start growing back) or if your body can no longer handle the toxicity of a particular chemo.

For stomach cancer, in addition to the 31 approved first-line treatments, there is also the option of participating in a clinical trial.  In a nutshell, clinical trials exist to test the effectiveness of new drugs that have not yet been approved.  There are several different phases of trials, and some can be for drugs that have already shown some promising results.  So that is an option that needs to be considered in most cases.

A clinical trial can be an attractive option for stage 4 gastric cancer patients for a few reasons.  First, the prognosis on the existing chemos is not good enough.  Second, most of the trials use one of those existing chemos plus the trial drug, so the odds are that your worst case scenario on the trial is somewhat similar to your prognosis on a standard regimen.  The third reason is the toughest to accept, especially early on after a diagnosis.  But the fact is that because stomach cancer is a rarer type of cancer, there are not as many subjects available for inclusion in trials.   Participating in a trial helps forward the cause towards finding better treatments.  Once we learned these things about trials and gained a better understanding of the benefits of participating in a trial, we really wanted to get Megan into one.  But by that point she had already started her regimen of first-line treatment, and she wasn’t eligible for any current trials.  Let me explain.

When Meg first checked into the ER, aside from the abdominal pain, she was doing reasonably well (at least as well as you’d think someone with very advanced cancer could be doing).  I swear that the doctors in the hospital were shocked after reading her chart, then walking into the room and seeing Meg looking so healthy.  But during the next two weeks, her condition starting heading rapidly downhill.  The local oncologist wanted to get Meg started on the EOX treatment, but we were trying to obtain as many opinions as possible.  We made an appointment with Georgetown, we got a remote opinion from Massachusetts General thanks to a family friend, and I was calling Johns Hopkins every day (that’s a story for another post).  But Meg started getting so bad that we decided we just needed to get her started on something.   We got the second opinion at Georgetown, and they had a trial available for Ramucirumab.  In retrospect it probably would’ve been a good trial to do, as the preliminary results have since indicated that it provides a small benefit over the current standard of care.  We asked the doctor if we should do it.  We wanted him to say yes, or give us some sort of recommendation one way or another.  He didn’t.  He said we could do it if we wanted to.  That wasn’t very helpful.  So we decided to move forward with EOX, which is one of the more popular regimens, and the one that she could get started on the next day at our local hospital.  If we went to Sloan Kettering or Johns Hopkins they likely would have recommended a different treatment, albeit one with much more intense side effects (mDCF).  Or maybe they would’ve had a different trial available.  

But even with the benefit of hindsight, we still don’t know whether or not Meg would have responded as well to the trial or mDCF as she did to EOX.  Every patient is different.  I watched a presentation by Dr. Ajani from MD Anderson, one of the most respected gastric oncologists in the country, where he relayed how tough it is to predict which chemo will work best for each individual patient.  He said he could have two patients whose cancer presents exactly the same way, give them the same chemo, and could very well expect the results to differ significantly.  So we definitely didn’t have regrets about going forward with EOX.  To better illustrate this, here is a draft post that Megan wrote on January 6, but never got a chance to finish:

As I mentioned before, I consider myself lucky that I have responded so well to chemotherapy.   I am able to hang out with my family and friends, go out to dinner, run errands on my own, and even work out on occasion.  When I first started chemo, it didn't seem like any of this would be possible for a while.

I was so sick and in so much pain right before starting chemo.  It's amazing how fast I got so sick.  I had pain from the beginning, but I started to feel worse on July 4th - a week and half after I was first in the hospital.  My liver was barely functioning and fluid was collecting in my abdomen.  I didn't know this until July 7th when I ended up back in the ER because the pain was so bad.  I started chemo four days later, but I barely remember that day.   

I was in so much pain that my doctor had prescribed a fentanyl patch to try and make me comfortable.  I had been on Oxycontin twice a day with Oxycodone as needed in between, but it did little to help the pain.  I tried Dilaudid next, and that helped, but it is such a short acting drug that the pain came back in just a few hours.  Adam called a bunch of pharmacies until he finally found one with the fentanyl patch in stock.  I started with the patch on July 10th, the night before I was supposed to start chemo. 

The next morning, I couldn't get out of bed.  I was so out of it that Adam ripped the patch off me and practically had to carry me to chemo.  As I said, I don't remember much of that day, and I have faint memories of the two days after.   I was at the hospital every day.  The doctors were giving me fluids to hydrate me and were checking labs (mainly liver function tests).  My liver still wasn't functioning well, so my abdomen was getting bigger and bigger as it filled with fluid.   I didn't recognize myself in the mirror - my arms and face were skinny, but my abdomen, legs, and feet were so swollen that I couldn't wear any of my clothes.

Then, on the night of July 20th, my liver started to work again.  Overnight the swelling that had gathered in my abdomen, legs, and feet went away.   It was such a great feeling to know that my liver was functioning again, that the chemo seemed to be working, and that the pain the swelling had caused was gone.

I think that post conveys how Meg was feeling.  She really wasn’t in a condition to be weighing the pros and cons of treatment options.  And my April 19 post detailed what I was going through, and how those first few weeks were so overwhelming.  We made the best decision that we could and I don’t regret it.  But what I would recommend to others would be to call a foundation that can provide you with impartial advice.  If I had found out about Can’t Stomach Cancer or No Stomach for Cancer then, maybe they could’ve gotten a top doctor at Sloan or Hopkins or MD Anderson to review her case.  That’s part of what their mission is – to be a resource for patients currently fighting this disease.  There’s no way to know for sure whether it would’ve made a difference, but at least I would’ve had some additional assurance and peace of mind that we were doing the best we could.

Ok, so the point of this post is supposed to be to relay why the first-line treatment you choose for metastatic stomach cancer is so critical.   It’s because as soon as you get started with a particular line of chemotherapy, your options for additional treatments become much more limited.   To begin with, you are essentially married to your first-line treatment until it stops working.  Soon after Meg got started on EOX, I read about a trial for a drug called a CMET inhibitor that supposedly was promising.  I walked into our next appointment with our oncologist armed with my notes, thinking we would have a detailed discussion about whether it makes sense to switch to this new drug.  To my surprise, he managed to knock it down without even seeming like he considered it.  What I learned later is that the CMET trial was only for patients who had never received chemo before.  So Megan was ineligible.  If she had walked into the ER in September instead of June, she would have been put on the trial instead of EOX (assuming she passed the tests for it).   But at that point I didn’t fully understand that, and I was frustrated with our oncologist, figuring we had to go to a bigger hospital where they would be more aggressive.

But then in November we went to Sloan and Georgetown for more opinions, and they said the same thing.  Actually, at Sloan I never even made it down to the CMET section of my notes.  The oncologist there spent most of our consultation telling us how Meg was having a tremendous response to EOX and that it would be “unethical” for him to recommend major changes, as there was no guarantee that something else would work any better.  In our mind the problem was that even though the scan she had done the previous week showed smaller tumors in her liver than two months earlier, the tumors were still there and the tumor markers had started moving in the wrong direction.  We didn’t want to just “keep the tumors under control.”  We wanted to be really aggressive and try to hit the tumors with something else.  But to the oncologists, even if the tumors are still there, as long as they aren’t getting bigger and the patient can handle the treatment, that’s considered a success.  We talked to four different oncologists (including one at Hopkins in January) and none of them would put her on different drugs until the current ones stopped working.  Unfortunately, this cancer is so aggressive that once a treatment stops working it is often too late.  For Megan, when the drugs stopped working it meant that her liver condition started spiraling out of control, and at that point she didn’t qualify for any trials because her liver wasn't healthy enough anymore (plus the limiting factor that she had already had a first-line treatment).

So, again, my point is that the first-line treatment for an aggressive, advanced cancer is something that should not be rushed into without getting at least one second opinion from a comprehensive cancer center.  But it can be very tough to figure out how to make decisions those first few days after getting the diagnosis.  So instead of spending all your time on the internet trying to become an expert on the different treatment options, spend your time finding a foundation with a good patient education program.  They can put you in touch with the right people and make sure you are asking the right questions.