Happy 71st Birthday Mom – Inspirational Patient Role Model and Immunotherapy Pioneer
Some posts are closer to my heart than others. This one is very close – it shows what made me the patient-scientist-advocate I am today… and it comes down to Mom.
My Mom and I were abnormally close – so much so, I could have been called a “Mamma’s Boy” in my younger years. In fact I was called that (on more than one occasion) but it didn’t bother me because I knew it was true. I was close to my Mom. I think she was a big reason I felt homesick at times during early college even though I certainly loved living in Ann Arbor – it just never felt like home without her.
My first real “adult” transition in life was when I moved alone to upstate New York after college to enter a Ph.D. program in “Medicinal Chemistry” For those of you that don’t know (i.e. almost everyone reading this blog), a “Medicinal Chemist” is the type of scientist that designs/discovers/makes the “active ingredient” in medicines – i.e. the part of the pill that does the work! I had wanted to go into drug discovery since high school. This was really driven by seeing a number of people stricken by the horrible disease cancer. Even as a kid, cancer really pissed me off. I wanted to stop it from hurting people.
Originally I had wanted to be a doctor but I tended to faint at the sight of blood and I hated dissecting animals. Those seemed to be impediments to medical school ha, so I switched to a drug discovery career plan instead. Luckily I had a love of all forms of science, including both biology & chemistry – which set me up to be a chemistry and molecular biology dual major in college. As you might guess, medicinal chemistry is a field at the exact intersection of chemistry and biology, so things lined up nicely. Of course, the very first visitor to my new “adult” (grad school) solo apartment was Mom. We had a blast on that visit.
I focused on cancer therapy research in graduate school and Mom focused on being Mom. Even though I lived >6 hours away, I still saw her and my Dad quite often – every month or two. I remember excitedly telling her during a summer visit back home in 1998 about a major breakthrough in the lab on a cancer project I was working on. I think she was both excited and proud as I tried to explain to her the science behind it in layman’s terms. That summer vacation with my Mom & the rest of my family (and dog KD!) in my hometown on the shores of Lake Michigan was incredibly fun.
That was in the summer of 1998, my how life can change in a blink of an eye.
March 17, 1999
I was finishing up an experiment in the lab when the shared lab phone rang (no grad student cell phones yet). A co-worker yelled to me that it was my Mom. She had gone in for a minor surgery earlier in the day. I figured she was calling to tell me she was going home. Instead she was calling to tell me she had pancreatic cancer. This was a complete surprise that was noticed during her “minor surgery”. We both knew what the words “pancreatic cancer” meant. We both knew the widely cited statistics at the time: Six months. Left to live. She was only 54 years old.
I immediately dropped everything and drove home to be with my Mom. I was worried about how she was coping. Was she crying, depressed, panicked? I certainly was. I didn’t know what to expect. They didn’t cover “surprise Mom 6-month-life expectancy” in Grad School.
I am often asked, where did I get my optimistic, hopeful and at times even joyous approach to being a cancer patient? Well a picture tells a thousand words – see two examples below. This is Mom shortly after her surprise diagnosis. Mom is the woman with dark hair, the other woman is her close friend Kathye. The party napkin is what she showed me minutes after I walked in the door. I have kept it for >16 years.
This is how Mom approached her cancer diagnosis & potential 6-month prognosis – with as much vitality, zest and humor as her physical health allowed! Of course she had her dark times, we all do, but they were normally an exception and not the rule.
She is my fellow-patient role model each and every day.
After we made a whirlwind trip to the Mayo Clinic to attempt a (failed) surgical cure – Mom and I looked at each other. In 1999 there wasn’t even a chemotherapy option for pancreatic cancer. That is how bad the situation was. A relatively mild form of chemo “gemcitabine” was given to patients. It didn’t improve the 6-month survival stats but it was “palliative” i.e. it made some patients feel better by slightly reducing the size of their tumors.
You know you are in trouble when you’re told you have 6 months to live but that you could take chemo to “feel better”. How did Mom approach this? She was shaken like anyone would have been but she had an incredible strength (I believe buoyed by her strong Faith), fighting spirit and zest for life. She wanted to fight. But how? She and I talked about general strategies and she was convinced that she wanted to do a clinical trial. She asked if “Dr. Tom” could help find one for her (her small town oncologist was useless for this task…).
People that know me in recent years know how deeply embedded I am in the clinical trial world. This was how that all started. Not with a bang… nor a whimper… but with the sound of a just graduated grad student’s telephone modem dialing up AOL to access the brand new wild frontier of the web. Remember, it was 1999.
I searched for clinical trials close to Michigan (where my sister lived) or San Diego (where I was moving). Mom’s physical health was already starting to deteriorate a bit, so looking at the found experimental drugs’ mechanisms of action… in addition to “possible” activity, side effects were very much on our mind. Pancreatic cancer is very aggressive and she had no interest in enduring significant side-effects from a study drug to gain (if lucky) e.g. 1 extra month of life…
Something in Los Angeles really caught our eye however… near enough to San Diego to do. It was a very small, research oncologist led trial (14 planned patients) of a new way to fight pancreatic cancer, using the immune system. Yes – it was an early cancer immunotherapy trial. These are all the rage in 2015 – but in the 1990’s they were on the fringes, especially for solid tumors like pancreatic cancer. I explained to Mom the details of how it was hoped to work. She looked at me and said “I think I should go for it – what do you think?” I said I thought she should go for it too.
Most of you who knew Mom probably had no idea that as a side-story to her life, she was one of the cancer immunotherapy pioneer patients in clinical trials.
What was the trial? Well due to the wonders of the net, you can still see it here: NCT00002773 “Vaccine Therapy, Chemotherapy, and GM-CSF in Treating Patients With Advanced Pancreatic Cancer”. How was it meant to work? I’ll actually tell the details to make a point. Basically the trial used pancreatic cancer cells as a therapeutic vaccine to try to train her immune system to attack her tumors. The vaccine was incubated with interferon alpha to make it more immunogenic, i.e. attract the attention of her immune system. Mom was given a low dose of a chemo drug called “cyclophosphamide” which, with essentially no side effects at low dose, can kill off “regulatory T-cells” to block them from suppressing the immune system in/near tumors. She was then also given a broad immune system stimulant called “GM-CSF”. She had no major side effects from the treatment.
What I find pretty amazing is that this protocol conceptually contained the general components successfully being explored as immunotherapies in 2015. 16 years of research since 1999 has made incredible advances by changing important details, but the concepts are the same: 1.) Make something more immunogenic to get the immune system’s attention. 2.) Remove immunosuppressors from in/near tumors 3.) Add an immunostimulant. In fact, there is an immunotherapy drug combination which has been named a “FDA breakthrough therapy” for pancreatic cancer due to promising signs of clinical activity in preliminary clinical trials! One of the components of this therapy is the GVAX vaccine which contains GM-CSF and is conceptually similar to the vaccine Mom got. It is now being dosed with another vaccine component, low dose cyclophosphamide to kill off immunosuppressive regulatory T-cells and in one treatment arm a “PD-1 inhibitor” which stimulates the immune system by releasing the brakes on it.
The details have important differences but conceptually, Mom was >15 years ahead of her time! Not bad for a dial-up modem and a Mom-Son team trying to figure things out as they went along….
Did her 1999 immunotherapy work? We’ll never know. It was a small study (14 patients), there was no control arm to compare against – it wasn’t even ever published. Mom’s life expectancy was 6 months. She more than doubled that to live 13 months. This could have been a coincidence but on an emotional level, I like to think that she and I made the right decision and the immunotherapy helped. We certainly had some fun months in southern California as she lived with me and commuted up to LA for the in-patient trial every couple of weeks. After helping my sister Anne with her end of life care, Mom died on Good Friday, 2000 at the age of 55.
Mom was born on September 13th, 1944. Today would have been her 71st birthday.
Now you can see how Mom and her story are so incredibly intertwined with my own. She was my first experience in figuring out clinical trials and my first exposure to the (then) unknown excitement of immunotherapies. Care-giving for her & her death were incredible inspirations to me to further make me driven in my professional career on cancer drug research. Most importantly, as a fellow-patient, she inspires me daily in terms of how I approach my own disease with Faith, humor, vitality, exuberance, and the guts to follow an unbeaten path while reaching for a cure. She is a tremendous role model that I strive to live up to everyday.
I guess I’m still a Mamma’s Boy. Happy 71st Birthday Mom.
Note Mom enjoying a cancer patient retreat and some BIG TREES – she & I are pretty alike 🙂