Friday, April 24, 2015

The Emperor of All Maladies and me

Naomi reflection with Ann Arbor skyline
I looked forward to seeing the title series on PBS but alas, I fell asleep during each of the 3 nights. Not to worry, it should be On Demand but alas, it was not. Shoulda, woulda dvr'ed it.

Nor have I read the book despite many recommendations.

For those who live under a rock, the Emperor is cancer. The series dealt with  the history of its treatment starting with childhood leukemia, a previously 100% fatal disease. Sidney Farber in Boston decided to give these doomed children aminopterin (ah, the Merck Index clogging up my bookcase finally came in handy in spelling this correctly. It also adds helpfully, that this is a rodenticide) which led to remissions. What the series did not say is what made Farber choose that particular chemical and how it worked, a weakness with this series. They no longer use aminopterin but instead its less toxic derivative, methotrexate which is still used in many cancers today (along with rheumatoid arthritis and psoriasis). What is the difference between a cancer cell and a normal cell? Sadly, what is needed to kill the former will kill the later but there are subtle differences. Cancer cells are much more dependent on growth factors, the first identified was folic acid. If one could block the production of folic acid by destroying a key enzyme dihydrofolate reductase, maybe one could slow or better yet, kill the cancer cell. This strategy had been used in the past to kill the malaria protozoa once it has invaded. Unlike bacteria, protozoa are eukaryotes just like our cells. Even though we don't seem to have much in common with a single cell organism, our chemistry does. What kills them will harm us. Thus there was a considerable overlap with antimalarials and early cancer drugs.

They did discuss the use of 'mustards' in chemotherapy. Soldiers in WW1 exposed to mustard gas had decreased white blood counts. A light bulb went off. Patients with leukemia have too many white blood cells. Maybe exposures to mustard gas will make things right? But mustard gas has many toxicities so 'kinder' mustard derivatives were made and used with some success. By the mid 1970s, leukemia was no longer 100% fatal along with a few other fast growing childhood tumors: a bit of success. Maybe if we throw more money at it, we will cure cancer. Thus The War on Cancer as proclaimed by Nixon and later on by a few other Presidents.

This is how I got a job in 1976, though by that time, Nixon was gone but the War on Cancer was still on. The National Cancer Institute provided all sorts of grants to universities and drug companies to develop new agents. I was employed on one of these contracts making kinder mustards, less toxic methotrexates, less toxic Red Devil derivatives. I developed a fairly complete idea where chemotherapy stood in those days, which in comparison to today, was really the stone age. We developed new agents that disrupted DNA replication in a whole variety of ways. Eventually the company decided that cancer was too difficult of a target and cut its workforce considerably. I was reassigned to a new area in 1986.

Thirty years later, when I found myself plopped dead center in Cancerland, I was treated with many of these primitive agents that killed the 'good' along with the bad though Taxol was discovered later. I can not keep track of al the new approaches out there these days. Lots of success with monoclonal antibodies that target specific cells: Herceptin for breast cancer (20% overexpress a certain oncogene which used to make this cancer particularly deadly but now curable) and Rituxan for B cell lymphoma. But yet again, this week I was reminded on far we have to go. I read the obit of another classmate from my cooking class. Dead from Stage 4 breast cancer. She had 12 years of symptom free existence before it returned 2.5 years ago (no one can ever say that they are completely cancer-free; at best one shows No Evidence of Disease but who am I to be a buzz kill). She had been on a clinical trial with a very promising drug from my former company, which amazingly is a traditional small molecule (versus a biologic such as Herceptin). What is more amazing, is that it was discovered quite some time ago, but was not developed until recently but better late than ever. There is such a need for effective agents that extending a life on the average of 3 months is considered a success. This one increases ones life span a whopping 21 months, which is a huge number. In her case, it had been 18 months or so. She seemed fine back in December when she last came to class. She seemed more concerned that a daughter was diagnosed with cancer than with her own travails.

Surgery had been the first line treatment of cancer long before chemotherapy. They went into detail about the Halstead procedure which was basically to remove not only the breast but the underlying chest muscles at the first sign of breast cancer, no matter what grade the tumor cells were. This was done thinking that breast cancer spread into what was physically closest completely ignoring where breast cancer usually spread (bones far away, liver also far away, brain far away) If breast cancer cells travelled through the lymph system or the blood system, the chest muscle removal would not help. Women soon stood up to their doctors refusing mastectomies opting for lumpectomies  instead. Change was slow; critical thinking seemed absent in the medical field. Thank you previous patients for refusing to be needlessly mutilated.

They did discuss a case of triple negative breast cancer that I fell asleep during: A young, Black breast surgeon who fought considerable odds to become a doctor, presented with it (more common among young African-Americans; I am not the usual patient). They rattled through the hopelessness of this diagnosis (always heart warming to hear) but damn, I didn't find out what happened to this woman. Readers, particularly my TNBC friends, help me out.

Back in the land where spring had lasted only 3 days and then it was back to winter, everything was covered in frost this morning. My hummingbird feeder frozen. Yep I put one out there ever hopeful. One of the many maps online (and not consistent with each other) showed sightings of the hummers this far north. I had planned a lunch on a patio with a friend yesterday only to have 30 mph winds and temps to match smash that dream. Lunch was fun enough looking out the window. But the winds have stopped, I put the bird bath out, the hummingbird feeder is thawing and it will be warm enough again to ride my bike this afternoon.


Lisa said...

I missed the series myself, so I can't help you. I think that my total naivetivity about what those drugs were and how they worked probably worked in my favor. I don't know if I would go through chemo knowing what you do about them.

I'm very sorry to hear about your friend. It is so hard to see this disease take so many people. That she'd been NED for 12 years throws cold water on my little party. I am 11 years out and beginning to feel the safety of distance. The reality is that we will never say cured.

Holly said...

It was hard to watch but I'm glad I did. the young breast surgeon survives and does well.

madness said...

I think you can watch all episodes here:

Sue in Italia/In the Land Of Cancer said...

Thank-you Holly and Madness. I'm glad the doctor survived. I didn't mean to throw water on your party Lisa. I have to think that it is very rare to come back after so long. A new primary popping up is far more likely, scary in itself but not so deadly.

Snowbrush said...

It was a good series. Since, for some time now, I've been living with the possibility that I have prostate cancer (I won't submit to a biopsy just yet based upon government recommendations, which are at odds with urologists’ recommendations), I wish they had talked more about that. I understand that it kills more men than breast cancer does women, yet the series spent a night on breast cancer and only a few minutes on prostate cancer.

Before synthetic taxol was created, it was obtained from the bark of the Pacific Yew Tree, a tree that was at risk in my area because people were going into the woods and stripping the bark, leaving the trees to die. They did this because good money was made from selling the bark, no questions asked.

Sue in Italia/In the Land Of Cancer said...

Snowbrush, I will be going to a funeral in a few days for my neighbor who died of prostrate cancer. He had no symptoms but his PSA in a routine check up was through the roof. He had a high grade tumor but most men diagnosed with intermediate grade live in a no man's land with the cure being worse than the disease and as you hinted, PSAs are no longer recommended. There are as many cases of prostrate cancer as breast but the treatment is far less clear. I wish you well considering what to do along with your incredible struggles getting relief from your pain.


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