Chemotherapy: Picking a Regimen

(In my case, ACTH, TCH, or clinical trial?)

The choice of which chemotherapy regimen to take was a very difficult one for me, because all options carry risks.  Unfortunately, clinical medicine can be more of an art than a science- ultimately it comes down to personal preference which option is the best.

Phase 1: Surgery

I have Stage 1B triple-positive (ER+/PR+/Her2+) invasive intraductal carcinoma, grade 3. My tumor strongly expresses all three receptors. I was tested for both BRACA1&2, as well as the BART rearrangement; all were negative. Had I been BRACA-positive, given the risk of recurrent or secondary breast cancer, my plan was to opt for a double mastectomy with reconstruction, however, as I was BRACA-negative, I chose to opt for a lumpectomy with radiation. I love my breasts, and, as lumpectomy plus radiation, if anything, has better long-term outcomes than mastectomy. Additional studies have similarly found no benefit of mastectomy versus lumpectomy plus radiation, even in younger patients. Furthermore, lumpectomy is associated with better long-term quality of life and lower rates of loss of sexual desire than mastectomy (I am a young married woman in a healthy, happy marriage. I want to keep it that way!). So, given no survival benefit to mastectomy and clear upsides to lumpectomy, I opted for lumpectomy.

Phase 2: Chemotherapy 

Given my age, my stage of disease, and the characteristics of the tumor, I was given the choice of either ACTH (adriamycin/cytoxan/taxol/herceptin) or TCH (taxotere/carboplatin/herceptin). While the jury is still out, there appears to be perhaps a slight advantage to ACTH in terms of breast-cancer recurrence (this is not statistically significant, even among patients with more advanced disease than I). Unfortunately, the ACTH also comes with an increased risk of heart failure and leukemia. These risks also do not take into account the subtle heart disease that may occur with adriamycin; we simply do not have enough long-term data to answer that question.

Cardiac Outcomes with Adriamycin and Herceptin

There is clearly an increased risk of heart failure with the combination of adriamycin and herceptin. Typically, this risk is quoted as a 4% rate of heart failure, however, may be higher, particularly in older populations and patients with pre-exisiting hypertension. Herceptin alone carries some risk, however, the cardiotoxicity associated with herceptin is primarily reversible.

In addition, these numbers do not take into account subtle changes in cardiac function that are of undetermined clinical significance. In other words, a large proportion of patients who receive adriamycin experience a decrease in the output (known medically as the "ejection fraction") of their left heart. This decrease in functioning may have no clinical significance, or may manifest as a problem many years down the line. The key point is that there is clearly a change, and there is simply not enough data to determine if this change will have an effect on quality or quantity of life down the road-- cardiovascular disease remains the number one killer of women, which may be why more recent data suggests that drinking alcohol after a breast cancer diagnosis may actually be associated with decreases in mortality, despite a trend toward an increase in breast cancer recurrence.

Another consideration is that, while there may be a slight advantage to ACTH versus TCH in terms of breast-cancer survival in clinical trials, in real-world practice, due to the combined cardiac toxicities of ACTH versus TCH, patients with ACTH are less likely to receive 12 months of herceptin, and longer duration of herceptin therapy is associated with improved outcomes.

Calculating the Risk-Benefit Profile of TCH versus ATCH for me: A Basic Clinical Decision Analysis

Each phase of breast cancer treatment is associated with some reduction in recurrence. Below is a rough estimate of the benefits of each therapy, with some risk of harm included. Note that I am including in this rough decision analysis a potential benefit to ACTH in terms of breast cancer recurrence, even though clinical trials have shown no difference between the two groups. This effectively biases the analysis in favor of ACTH. I did not include the risk of heart failure for herceptin alone (0.5%) because this risk is the same in both the TCH and ACTH arm, and thus falls out of the analysis.

Tamoxifen: 50% risk reduction
Herceptin: 40% risk reduction
ACTH: 30% risk reduction
TCH: 25% risk reduction

So, let's start with a 25% risk of recurrence prior to starting any treatment...

... With tamoxifen: 12.5%
... Adding herceptin: 7.5%
... With ACTH chemotherapy regimen: 5.25%
... With TCH regimen: 5.63%

Now including the other potential harms of treatment:

ACTH: 1-8% risk of heart failure (this risk is regardless of risk of breast cancer recurrence, and is higher in patients with pre-exisiting hypertension)
ATCH: 0.1% risk of leukemia

ACTH: 5.25% risk of breast cancer recurrence + 1% risk of heart failure + 0.1% risk leukemia = 6.35% total risk adverse outcome

TCH: 5.63% risk of breast cancer recurrence + 0% risk of heart failure + 0.1% risk leukemia = 5.63% total risk adverse outcome

So, in this case, the risk of harms other than breast cancer tip the optimal risk-benefit profile in the favor of TCH. If the risk of breast cancer recurrence were higher, assuming that ACTH is, in fact, more effective against breast cancer than TCH, then the optimal choice of chemotherapy regimen would change.

Note that I did not model all types of risk-- just major ones (ie, I only included heart failure, not subtle changes in cardiac function). I also weighted breast cancer recurrence, heart failure, and leukemia all as equally "bad" adverse outcomes, which is probably not fair (leukemia should probably be weighted much, much more strongly).

My choice

By now (even if you have read no other part of this blog), you have probably figured out that I chose TCH. There is no statistical benefit to ACTH, and clear harms (in terms of cardiac toxicity, long-term quality of life, and leukemia).

My parents had a really, really hard time with this decision. They felt strongly-- and put a lot of pressure on me-- to opt for ACTH, because they were/ are both scared out of their minds about my diagnosis.

My take on it is this: Why would I ever take a definite harm for a probable no-benefit? Simply put, that would be insane. Had my risk of breast cancer recurrence been higher, I would have had a really hard time with this decision. But any conceivable benefit of ACTH in my case is outweighed by its definite harms.

Patients, in general, tend to over-estimate known risks and tend to under-estimate risks that are unknown. In my opinion, picking ACTH is favoring fear of a known risk (ie, breast cancer recurrence) over unknown risks (ie, leukemia and heart failure). As a physician, I assure you, there are far worse things than breast cancer recurrence (and immediate, treatment-refractory leukemia certainly applies. Heart failure is also no cake walk).

Ultimately, picking a chemotherapy regimen comes down to a question of personal preference and weighing risks. If you are in the unfortunate situation of having to chose, think about what scares you the most and how you want to live your life.... After breast cancer. I want to be able to climb Mount Kilimanjaro with my husband-- and I sleep at night knowing that my heart is in good enough shape that I still might be able to.

A Foot Note on Clinical trials

I did consider two clinical trials, and had I been a good candidate for either one, I was leaning toward participating. The first trial is comparing adding a second monoclonal antibody to herceptin plus chemotherapy. Pertuzumab has been shown to prolong survival in the metastastic setting. I was put on the wait list for this trial, however, given my nodal status was considered on the border of being "too low risk," the wait list was very long, and I did not want to delay treatment for months only not to be enrolled (initiating adjuvant therapy longer than 12 weeks post-surgery is associated with worse outcomes).

The second trial, the ATEMPT trial, is a Phase II trial comparing taxol/herceptin to a kadcyla, a novel "smart bomb" that was recently found to improve disease-free progression in the metastatic setting, but data in the adjuvant setting are limited. I was strongly leaning toward joining the trial, but when the tumor board* recommended against it, I decided to go with a standard regimen. At the 11th hour, some members of the tumor board did reverse their original position, but, at that point, I had long accepted losing my hair and did not want to delay treatment any further.

*Tumor board is a group of physicians, typically consisting of some combination of oncologists, pathologists, radiologists, radiation oncologists, and surgeons who discuss clinical cases and attempt to come to a consensus decision for the best treatment course for an individual patient.

Quick Update: Patient Advocacy and Navigating the System

Two weeks down to two days!

After much to do, I was able to secure an allergy appointment yesterday via the phoning a friend method of speeding things along (see yesterday's post on navigating the system). I could not be accommodated at BWH for a week, so I walked across the street to BIDMC and received immediate care. The allergist I saw was fantastic, and called over to BWH to expedite my infusions, for which I am extremely grateful.

With her help, and the heroic efforts of my primary providers, as well as from nursing providers in the desensitization unit, I was able to secure an appointment for my infusions today, which reduced my delay in treatment from what was looking like two weeks, to only two days. 

Downstream effects

Unfortunately, I cannot get back on my original schedule, which pushes the next infusion back by five days, which pushes back my radiation by a week, which means that 1) I will not be able to complete chemo and radiation by the new year (psychologically, I was hoping to leave this mess in 2013, and start fresh in 2014), 2) my move is delayed, and 3) I may not be able to make my delayed start date for my new job. Not to mention how this affects my husband going to his board review course (which now starts the day after my next infusion, as opposed a week later, when I am more able to take care of the kids), my own patients, and all of the other aspects of my life that are not cancer-related. 

I am still waiting to receive an apology from the nursing staff ultimately responsible for the delays. Further, no one has offered to at least give us free parking on the day of the error-- that cost, and the healthcare costs associated with the event, all fell on me (not to mention personal costs, which I outlined in my last post). 

Cancer is NOT my life.

As much as possible, I try to make sure that cancer does not rule my life, but rather is a hiccup in an otherwise full and happy existance. Events like this one make that very, very difficult. I am quite sure that the powers that be who were responsible for this mess will claim that this was a "patient safety issue--" but it was not. It was a communications error, and an error that occurred due to vacation scheduling. My life has already been upheaved enough by this diagnosis and treatment. I do not need additional (and unncessary) obsticles thrown in my way. My new goal (pathetic as this is) is to be able to actually taste Thanksgiving dinner. We will see if I get there.

Small victories: You can make a difference!

I am still waiting to hear back from the patient representative, however, on the plus side, it sounds like the Farber is working on putting a new system in place so that this does not happen to other patients. If I can prevent this torture from happening to someone else, I will count this whole thing as a moral victory.

Puppy love 

As for my family, in the middle of all of this mess, we decided to get a new puppy. We need a little joy in our lives! I am thinking of smugling him in in a bag and claiming he is a therapy dog-- hey, it works in New York City restaurants! I'll have to check Ebay.

Health Care Quality Snafus, and the Cost of Medical Errors

Infusion #3: Date TBD

In general, I try to keep my emotions relatively in check, but I was pumped full of steroids and had a very irritating day-- and I am an insider who knows how to navigate the system. I cannot imagine how frustrating the day would have been if I did not have an idea of how to move things forward.

The recap: I arrived at the Farber on time, then waited for over an hour in laboratory services to have my blood drawn and an IV placed (apparently, they misplaced my lab orders-- again).

I then saw my provider, got a green light, and was shuffled to another waiting room where I waited for about an hour and a half before being informed that, after taking steroids, having my blood drawn and an IV placed, taking off of work, arranging my life to get chemo, and getting emotionally prepared for another round, I would not receive my infusion today due to the need for allergy clearance.

The million dollar question is: Why this was not brought up three weeks ago (when it could have been addressed in the interim) but rather first mentioned after all of these other pieces had already been put into motion?

On top of the error (which I believe to be due to what we refer to in medicine as a "Swiss cheese" effect), the nursing manager was extremely rude to me. Given the circumstances (which were the hospital's fault-- not mine), I requested that she call allergy to try to expedite an appointment. She refused-- and told me that she would send out an email within the next hour or so. She then added on that I "should not expect to hear from her today, or even tomorrow." All of this while glowering at my husband and I.

There is long-standing evidence that, when nurses, physicians or hospital systems make an error, the safest course of action is to admit it and apologize (where I work, we even send flowers!)-- not to blame the patient and to be rude.  After all, this error affected a lot of people, and was quite costly (to me-- not to the healthcare system).

(A side note: My providers were excellent advocates for me, and, to their credit, bent over backwards to try to rectify the situation-- I remain extremely grateful for their excellent care and attention).

People very directly affected:

-Me
-My husband
-My children
-My nanny (who has to arrive early on infusion days)
-My nanny's husband, and her children
-My mother-in-law, who picks my son up on infusion days and makes sure he has a happy day and is distracted so he does not worry about me too much
-My boss, and co-workers
-My patients, who will now have to be rescheduled (one of whom needs pre-op clearance from me!)
-My friend from California, who is flying in to Boston, and now will not be able to actually see me due to appointment scheduling

People somewhat less directly affected:

-All of my cheerleaders (who help to get me through the day!) - my family, in-laws, friends, and all of the other people who have gone the extra mile to make me laugh or stuck their necks out to make things smoother for me
-My future boss-- I now may not be able to start on my (delayed) planned start date, because delaying chemo delays radiation which delays my move which delays my start date

.. And so on. You get the idea.

My (rough) estimation of the cost (to me and my family/friends) of this event:

- Cab ride (for me): $25
- Parking: $10
- Lost wages due to day off: $1000
- Extra childcare costs: $40
- Cost of unnecessary laboratory testing and IV placement: $300 (a guestimate)
- Cost of a round trip train ticket to NYC: $200
- Cost of delaying future patients: ????

Total one day direct cost (to patient): Greater than $1575

Note that I had been planning to go on vacation next week- and have paid for plane tickets, have a deposit on a hotel, my sister in law took off of school (to watch the kids), my dogs are being kenneled... And this estimate reflects none of that. The estimate also does not reflect a loss of wages for delay in my start date for my next job, or the mortgage that I am paying for a house I am not living in while I am getting treated.

Nor does it reflect the psychosocial costs of delaying treatment- which are not insignificant.

How I handled it:

A long time ago, one of my long-term cheerleaders gave me a card that read, "When like gives you lemons... Make margaritas." While I did not bust out the tequila, I did actually take some lemons and make lemonade on a hot summer day. I also saw my fabulous trainer, Tara, who helped me to work out my aggression at the gym, and has been a great friend to me throughout all of this.

I then got on the computer and emailed key people, and got on the phone and started advocating for myself. My husband called the patient representative (see below) and I started calling around to my other doctor friends, until I was able to secure an appointment for allergy tomorrow and look toward moving forward.

So what are your options as a patient?

1. Talk with your direct provider- see if your physician can intervene on your behalf. I also recommend contacting your primary care physician, as your primary care provider should be one of your biggest advocates (and should have knowledge of how to navigate the system). A dirty little secret is that specialists require referrals from primary care physicians to stay in business... So a little push from your PCP can go along way (because if the specialist does not respond, the specialist stops getting referrals).

2. Call the hospital ombudsperson (also known as a patient safety advocate or patient representative). The hospital ombudsman is employed to listen to patient concerns, and to communicate these concerns to the powers that be about what happened, and what could be done to rectify the situation. Typically, concerns are reported to your provider, the supervisor of the person you are filing the complaint about, and someone with in the hospital's health care quality division.

3. Ask that an official quality "miss" or "near miss" report be filled out-- these reports are typically reviewed by the health care quality division within the hospital, and can lead to quality improvement reviews, to try to get to the bottom of how the error occurred, and to determine how to stop it from happening to another patient in the future.

4. Phone a friend. Doctors have their own sub-culture and no one knows more doctors than another doctor. Furthermore, because of the way doctors get into medical school, residency, and fellowship, doctors tend to get scattered far and wide. So, if you can call one doctor, chances are s/he knows someone who knows someone who knows someone where you live. And doctors listen to other doctors.

5. If the error is really egregious, or caused you to lose faith in the healthcare you are receiving, ask for a second opinion, or transfer your care. How you receive your care-- and who you receive it from-- is always in your hands.

Managing Reflux

Until I got pregnant, I honestly never thought much of reflux-- but it is awful! So here are some general tips for handling it. One bit of good news is that (unlike in pregnancy), with chemo, most of the reflux drugs are safe and available to you. In pregnancy, your only option may be Tums and that can be very tough...

Keep in mind that Tums acts the most quickly (5-20 minutes or so) but has the shortest duration of action, and can actually worsen reflux symptoms in the long-term. So, it is good for very short-term immediate control-- but not much else.

Pepcid (or other members of the H-2 class) work in a fast-to-intermediate time frame (1-2 hours), but have a somewhat longer duration of action.

Prevacid (or other members of the proton-pump inhibitor class) work in the longest time frame (3-4 days before full effect!) and so are not particularly useful for immediate relief of reflux. These medications are really designed for people with chronic reflux, or ulcers-- but not for short-term control.

What works the best for me is taking Tums as I need it (ie, if immediate symptoms are very bad), and then taking an H2 blocker twice daily for the duration of the reflux symptoms (for me, with TCH, this seems to be 4-5 days). I have not tried the proton pump inhibitors, because they take too long to act, given the duration of my symptoms (but might be useful if symptoms last longer).

Just remember- don't take something that will work in three days for a problem that is happening right now!!

Second Infusion

Quick update on second round of chemo (one third of the way there!)

I had my second infusion of TCH two days ago, second neulasta shot yesterday. And, I am happy to report, this round seems to be easier than the first. Maybe it is just because I have learned how to pre-medicate myself better, but the symptoms are not nearly as bad. Little to no neuropathy in my left hand (and no difficulties texting) and the terrible taste has not come on yet. The reflux would be there.. but pepcid is a great drug and so I am not feeling those effects so much.

Masking the Metallic Taste

I found that one of the worst side effects of the TCH is the awful burned/metallic taste that it left on my tongue, and the strange things that it did to my perception of taste. There are nutritionists who specialize in helping with finding foods that work while on chemo; below is just a list of what worked- and what definitely did not- for me. As I learn more, I will update more.

What tastes good:

Fried plantains. Seriously- taste exactly like fried plantains should!

Plain bread and simple crackers

Cheese that is not too salty

Mocha lattes (the chocolate seems to mask the bitter taste of the coffee)

Mint gum

Sparkling water, ideally with some flavoring (like a slice of lemon or lime)
Mangoes
Avocados
Tomatoes
Ice cream 

What does not:

Spicy foods- just tastes like eating a fistful of black pepper

Wine- tastes like Ever Clear! And I was not even into that in college..

Coffee

Plain water

Two weeks (or so) later...

Starting about 10-days post-infusion, I started to feel back to myself again. I did have some oral ulcers starting around 7 days post-infusion, but these were happily all gone after 3 or 4 days, and the burned/metallic taste on my tongue started to dissipate, as well. By 14 days post-infusion wine, coffee, and spicy foods were all tasting nearly normal, which was a great relief. Only other symptom of note was some temperature disregulation, but this was also gone by day 10 or so.

 

Since I was feeling quite well, I was away from the computer, and out and about. I was able to have a normal and full work out with my trainer, Tara S. at Healthworks in Back Bay (she is fantastic!) and then head up to the Adirondacks for a long weekend with my husband, kids, dog, and extended family. We spent the weekend hiking and hunting for dragons in remote areas of the world (or New York state, anyway). No dragons were to be found (my son thought the bears might be scaring them away. Interestingly, the dragons were also scaring the bears away), but we did find some toads and other wild life. It was very nice to spend a few days not being a patient!

 

As for my hair.. It is still on my head! The experts told me to expect it to start thinning and falling out around day 14 or so, and that it would gradually fall out and be entirely gone around the middle of the second cycle. My first goal was to have hair for my daughter's first birthday, day 7 (I did) and then to make it through week 2 with hair. I then crossed my fingers and hoped that I could see my cousins while looking reasonably normal and like myself, which also worked out in my favor. Then, on day 19, my daughter pulled on my hair and a clump came out. I was worried that I would have to shave my head by the end of the day, but today is day 20, and I am losing a few strands here and there, but nothing obvious (I also tend to shed quite a bit even under the best of circumstances). Given the hair pulling incident, I do not expect it to last much longer, but I am relishing every extra day I get!

 

Back for another round on Wednesday. Definitely not looking forward to it, but, on the other hand, at the end of the day, I will be a third of the way done- and that's almost half! Plus, this time around, I have a much better idea of how to handle a bunch of the side effects, so hopefully it will be a bit easier. Eyes on the prize!