Chemotherapy 101

20130216-185610.jpgWhen I was first told that I had to undergo extensive chemotherapy, I wanted to find out all there is to know about what it was and how it worked. I have a good grasp of organic chemistry, including platinum chemistry, but I still had some gaps I wanted to fill in. I expected my oncologist to provide the answers. After all administering chemo is their main business and pretty much all that they do so they have to know all there is to know right? WRONG! Unfortunately I found out how little most oncologist know about chemotherapy. I guess If they were like me, they were too drunk to attend many of their Oncology 101 lectures.

My main question was quite simple, “how long does oxaliplatin keep killing cells after the infusion?” The first answer I got was 14 days. This happens to be the length of the chemo cycle. Well I knew this was rubbish and the oncologist did not know and just took a guess. Second oncologist was no better, but at least he had the guts to say “I don’t know’ but will find out” (he never did). I needed to know how everything works, so that I could dose the various supplements that I was taking so as not to interfere with the chemo action. I found no help from any of the oncologists I had spoken with and had to rely on my own research.

5FU

5FU (Fluorouracil) is part of both the folfox and folfiri chemo regiments. 5FU is an antimetabolite, and works during the S phase of cell division. S phase is the step where DNA is replicated in preparation for cell division. 5FU has to be inside the cell during the S phase to have an effect. This is why it is typically given over two days via pump. 5FU has a very short half life, about 15 minutes, so it does not stay long in the blood stream. (hence the continuous pump). What it means is that in about 12 hours after the 5FU pump is disconnected, 5FU is pretty much done.

Leucovorin

Also known as Folinic Acid, it is given as part of both folfox and folfiri. Its function is to make it easier for 5FU to get inside cells. Its similarity to folic acid is why most oncologists recommend not taking this supplement during chemo.

Oxaliplatin

This is a real nasty. The active form of oxaliplatin has a half life of about 13 minutes in the blood stream, and has to enter the cells before it binds to blood antigens and proteins, which it does readily. Once oxaliplatin binds to blood antigens it become innefective. What an oncologist will not tell you is that the platinum will stay in your system for many years, and can still cause DNA damage years later. Think of Mercury poisoning, Platinum is not much better. There have been no long term studies on Oxaliplatin and even 5 years later your platinum levels will likely be 30 times the norm.

Oxaliplatin does not depend on a specific cell cycle. It works by enterng the cells and binding with DNA strands, creating crosslinks. The cells can not unwind the DNA strands and this triggers cell death through apoptosis (self induced programmed cell death). Oxaliplatin has a limited use however. Typically either the neutropathy the drug causes means that you have to discontinue the treatment, or the cells will mutate and develop a better repair mechanism. Basically the cells will learn how to excise the crosslinked DNA, and repair the damage rendering oxaliplatin ineffective there after. Typically oxaliplatin is useful for about 6 months. So how long is oxaliplatin active in killing cells? My best answer: about 5 days.

Irinotecan

Irinotecan is part of the folfiri chemo regime. It works during the G1 phase of cell division. This is the phase where DNA unwinds. Its main function is to inhibit DNA replication and transcription. The half life of Irinotecan is much longer, up to 12 hours which means it will remain active for about 3-4 days after infusion.

Avastin

Avastin is the trade name for Bevacizumab. It is a monoclonal antibody and its often given in combination with Folfox and Folfiri. Its function is to inhibit angiogenesis, which basically means it slows down the growth of new blood vessels which cancer needs for new growth. It works by inhibiting VEGF-A, a chemical signal that stimulates angiogenesis. The half life of Avastin is 21 days, which means it will remain active for several months.

Avastin can cause nose bleeds, internal bleeding in the digestive tract, hemorrhages and high blood pressure. Wounds will also heal much slower.

Chemo Summary

Chemotherapy is usually given in 2 week cycles. The first 5 days is when most of the damage is done, the rest of the time is a recovery period. The theory is that your normal cells can recover faster than the cancer cells. Chemo has the greatest impact on fast dividing cells, such as cancer, unfortunately there are other cells in your body that divide at a fast rate and the chemo does not discriminate. The cells that are most impacted include the cells lining your digestive tract, bone marrow, hair follicals, lining of your mouth and nose.

Chemotherapy Side Effects

What are the side effects of chemotherapy? The short answer is that there are many, but everyone responds differently. Before you start your treatment, you will be given a long list of potential side effects for each drug, or you can find a full list online. My side effects were:
Folfox + avastin: Neuropathy courtesy of oxaliplatin, constipation caused by leucovorin, nose bleeds and rectal bleeding due to avastin and ofcourse nausea.
Folfiri + avastin: Hair loss due to Irinitocan, otherwise the same as folfox, but without the oxaliplatin neuropathy. Nausea I noticed was a little worse. I will describe my chemo experience in more detail in another post.

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About Ren

I have been diagnosed with stage 4, metastatic colorectal cancer in October 2012, 3 days after my 44th birthday. There is no cure, but I am determined to go down the road less travelled to find one. I have setup this blog to document my journey and hopefully help others in the process. My view is that if there is a cure, it does not lie with traditional chemo, but with the immune system. Time will tell.
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