Combination Therapy, Motherfuckers!

So, here’s the thing about metastatic breast cancer treatment: you usually get one drug at a time. We call this single agent therapy. So, like, I’m on Xeloda right now, and that’s it. We get one drug at a time, and when that one stops working, we switch to another one, then another, until all the drugs are gone and then we die. This sort-of made sense when chemo was all we had, because being on multiple chemos at once makes you feel horrible. Wait, that’s not a strong enough descriptor of what it’s like, so picture this: vomiting every day, being to weak to get out of bed so you shit yourself, rashes, mouth sores, being able to die of a cold because you have no immune system to speak of…and that’s not even all of it. 

So, since you’re going to die anyway, I mean, why would a doctor put you through all that? The answer is, they wouldn’t. Instead, they try to buy you a few months here, a few months there, without ruining the average 33 month lifespan you have after your MBC diagnosis. 

This all made sense to me until I read The Death of Cancer, which blew my mind. Do you know why Hodgkins has a high cure rate nowadays? Because some doctors said “Fuck this, let’s just poison the shit out of this cancer until it’s GONE.” And they gave patients not one, not two, not three, but FOUR different chemotherapy drugs at once. It was called VAMP for short, and guess what? It worked. Because instead of just attacking cancer one way, they attacked it on multiple fronts at once. Instead of seeing the patients as terminal and trying to make them comfortable, these doctors saw the patients as people who should get to live normal lifespans, and they set about to make it happen.

After reading that book and talking to some smart cancer researchers, I’m now convinced that combination therapy is where it’s at. I see how the story ends for my friends who run out of drugs to try, or whose bodies become so fucked up by years of continuous single agent chemo that they can’t tolerate any further treatments. Fuck that. I don’t want to slowly decline for another year or two and then die. I want to send in all four branches of the military to fucking destroy the cancer.

I realize that this requires a dramatic shift in thinking for oncologists. Y’all have been trained that single agent therapy is the way to go because combination chemotherapy is brutal. And I bet it’s really hard for any of you with a conscience to watch your patients go through what combination chemotherapy can do to them. But, let’s talk about how little the outcomes have changed by just doing single agent therapy: in the last 40 years, the average lifespan after MBC diagnosis has gone up about a year and a half, most of which is spent feeling like shit anyway because even single agent chemo is pretty shitty. That’s it, 40 years of research, 18 months in improved survival. And, now we live in the era of substantially less toxic immunotherapy drugs. The time is ripe for a change of philosophy, from extending life a few months to turning our disease from a terminal one to a chronic one.

Apparently I’m not the only one who thinks this is a good idea, because I read today that Pfizer is planning to study a triple combination of immunotherapy drugs on patients with advanced cancer. IT’S ABOUT FUCKING TIME. I hope other Pharma companies and researchers will take this approach more often, so that it can start happening in the clinical setting ASAP. 

As always, my touchstone for cancer activism is how the AIDS movement made it possible for people with AIDS to live a normal lifespan. Know how they did it? Combination therapy. But it took them demanding better drug development and getting the people in power and the Pharma companies to listen for combination therapy to come about. I’m prepared to scale the walls of the FDA or the NIH if that would make the change happen–but I hope that it won’t be necessary, and that researchers will stop seeing us as dying, and start helping us live.

3 thoughts on “Combination Therapy, Motherfuckers!

  1. Beth,

    Absolutely spot-on post! In fact, I often think about the strides made with the AIDS movement and wonder why can’t the same passion be put into finding a cure for breast cancer? It’s mind-boggling. Thank you for this honest post.
    Beth Gainer recently posted…Dancing Alone on Mother’s DayMy Profile

  2. Thirty years ago, my wife did a pediatric clinical trial and endured TEN (Yes, 10!) chemo drugs over 18 months in the 1980’s. It nearly killed her, but the combination chemo cured her Leukemia.
    Today, she’s dealing with breast cancer.

    Yes, Combination Therapy works. Yes, Immunotherapy works. Combining the two will end cancer, someday.
    Getting the breast cancer industry to accept this notion is a different story.
    Imo, there’s so much dogma, organizational dysfunction and lack of strong leadership.
    As pointed out, targeted drugs like Kinase inhibitors, inevitably fail due to resistance, not before putting patients through a bevy of toxicity. The heterogeneity that exists, even in early stage disease, is vast. Cancer simply exploits the power of evolution to survive. Thus, a mono-therapy (single agent) approach will almost always fail.

    To quote the Emperor of Maladies, “if cancer exploits the power of evolution to survive, perhaps only a commensurate weapon, equally adaptable, also perfected over millions of years, can overcome it. That weapon many scientists believe is the human immune system”.
    (Skip ahead to the 1 hour, 11 minute mark of the video, for the quote)
    In other words, Immunotherapy is an approach that has the ability to survive as long as the cancer cell does and has the ability to evolve with the cancer. Harnessing the power of T Cells is a good example. If properly activated, T-Cells are a “living drug” against multiple targets and most importantly, they have a “memory” providing lasting anti-tumor effect. Not to mention, they can knock out cancer Stem Cells, the theoretical “root of all evil” and responsible for all recurrences.

    Today, there are 250+ Immunotherapy Clinical Trials for Breast Cancer (according to the Cancer Research Institute webpage). Whether or not patients enroll is a different topic.
    I’ll end by saying that it comes down to the researchers doing the basic science to discover how to make Immunotherapy more successful for solid tumors like breast cancer, especially ER+ disease, which has the unfortunate reputation of being “not very immunogenic”, an antiquated view that needs to end.
    Breast cancer Oncologists need to be reminded that Melanoma was also considered “immunologically silent”, but pioneers like Dr. Jim Allison fought the dogma and figured out a way to block the inhibitory pathway, CTLA-4, allowing the immune system to takeoff and beat Melanoma. This resulted in the checkpoint inhibitor, Yervoy. Before Yervoy, the median survival was ~7 months for metastatic Melanoma. Now, it’s extended to ~5 years and that number will only increase as patients continue to be followed.
    The point is there are many more Immune system related inhibitory pathways waiting to be discovered, some of which are breast cancer specific and related to estrogen signaling. We need a “Dr. Jim Allison” type researcher in the industry to discover those pathways, so Immunoptherapy can be properly harnessed for the broad spectrum of metastatic breast cancer patients.

    – John Smith

    PS: Sorry for the long comment. If you made it this far, feel free to join the Facebook Immunotherapy group:
    Patients, caretakers, healthcare professionals, researchers, students and advocates are all welcome.

  3. Ill join you on the scaling. Can you imagine my larger than life boots climbing the walls at the NIH?! BUT I wanna live so my pride be damned!

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