Sunday, December 20, 2009

About Chemo

So people keep asking me about my chemo (mostly medical types but also normal people) so this entry is intended to be a primer.

The clinical trial in which I am participating, GOG-252, has 3 arms. The first Arm is mine, and uses only standard intravenous (IV) therapy. The other 2 arms also use standard intraperitoneal (IP) therapy.

In Arm 1 I will receive 6 cycles of standard chemotherapy, each cycle 21 days (3 weeks) long.

Each Monday of the cycle (days 1, 8, and 15 which for me on my first cycle are Dec 7, Dec 14, and Dec 21 (tomorrow) I get a standard drug called Taxol (generic name Paclitaxel, also called Onxal) at a dose of 80 mg/m2 each Monday - total dose for the cycle is 240 mg/m2, which is actually a bit more than standard therapy. but since it is split into 3 doses (standard is a smaller dose but all given on the first Monday) there are fewer side effects.

Taxol belongs to a class of drugs called "plant alkaloids". As you probably guessed, plant alkaloid drugs are made from plants. Closely related drugs, the "vinca alkaloids" are made from the periwinkle plant. Since periwinkle blue is my favorite color, I like that idea. However, since they don't let you select your chemotherapy based on color preference, I am not taking one of those. Taxol is in a category of plant alkaloids called Taxanes, which are made from the bark of the Pacific Yew tree. Which actually still sounds pretty cool - rather hippie-oid I think. So I think of Taxol as my "flower power" drug and am trying to view this whole chemo experience as a second change at experiencing the 60's, since I missed important parts of that whole era the first time around by spending most of my time inside studying while every one else was outside, getting high, tuning in, and ... whatever - having fun and aging their skin.

Taxol and other taxane drugs work by interfering with the ability of microtubule structures within the cell to develop and function properly. Cancer is a problem because cancer cells lose the normal "brakes" on reproduction and just replicate themselves out of all proportion and reason, using up space and resources originally intended for other normal cells and ultimately just taking over, and killing off, the host. Not very considerate of them if you think about it. Microtubles (scientific name for lots of tiny little tubes) get generated and used as an important part of a cell's ability to divide and replicate itself. So by inhibiting (interferring with) these tiny little tubes that are inside cells and used to make new cells, Taxol interferes with the cancer cell's ability to reproduce itself and ultimately leads to cell death. Too bad for the little cell but actually very very good for me.

On the first Monday of the cycle (Day 1) I also get a second standard drug called Carboplatin (trade name Paraplatin)at a dose of 6 units IV (which is the standard dose).

Carboplatin belongs to a class of drugs alled "alkylating agents", also referred to as "cytotoxic" agents ("cyto" = scientific word for living cell substance and "toxic" scientifically refers to, well just what you would expect, toxicity or poison, so this is a substance the poisons or is toxic to living cells. or antineoplastic agents. (Again, "anti" is scientific short hand for "against" and "neo" is science talk for "new" and "plastic" is sort of science talk for living stuff so "antineoplastic" is a scientific phrase meaning this is stuff that works against new living stuff).

Carboplatin is an alkylating agent (antineoplastic or cytotoxic agent) that has most of its effect during the resting phase of a cell's life. Carboplatin is in a family of alkylating agents called "Metal Salts", so while i am unclear on exactly where they come from, I don't think it is from flowers. I suspect these are cooked up by chemists in artificial environments like labs. No flower power here. In fact, another group of alkylating agents are the mustard gas derivatives. Remember the terrible Gas attacks that troops experiences in the trenches of Europe during WW I? Or that Kurds in northern Iraq experienced under the command of Saddam Hussain's henchman "Chemical Ali"? Those gas attacks used Mustard gases. So that old gas mask up in great-granddad's attic was intended to protect him from things now being flung at cancer cells in a more targeted way.

Since Carboplatin has most of its effect during the resting phase of a cell's life, this means that while the first drug - my flower power drug Taxol, attacks cancer cells while they are trying to make additional new cancer cells by messing up the tiny little tublules inside the cell that the cells needs to reproduce, this drug, Carboplatin, works while the cell is taking a break and just resting. So the poor little cancer cells can hardly get a break since this combination delivers a one-two punch whether they are working to reproduce or just sitting around trying to rest and recuperate. (Actually I don't feel very sorry for the poor little old cancer cells and honestly, I don't really think you should either. If they were not misbehaving in the first place we would not be throwing alkylating agents and plant alkaloids at them in the first place.)

So the drill is this: Cycle 1 day 1 (Monday Dec 7) I get a big dose of flower power Taxol that attacks cancer cells while they are trying to reproduce by messing up all the tiny little tubules within the cells, followed by a big dose of my Alkylating agent/metal salt (closely related to that Mustard Gas agent floating over the WW I trenches) that attacks cancer cells when they sit down to rest.

A week later (Cycle 1 Day 8 - Monday Dec 14) I got another dose of flower power Taxol. And a week later yet (Cycle 1 Day 15 which is tomorrow Monday Dec 21) I get yet another dose of flower power Taxol. Which should make it pretty inconvenient for cancer cells trying to make more cancer cells.

Then the next week we start a new cycle with flower power Taxol + alkylating metal salt Carboplatin (Cycle 2 Day 1 monday Dec 28) to interfere with reproduction and resting, followed by 2 weeks of flower power Taxol alone (Monday Jan 4, and Monday Jan 11) to keep messing with those tiny little tubes within the cells.

Why, you may ask, do I get 3 doses that interfere with tiny tubules and cell reproduction for every 1 cycle that messes with the cell's ability to rest? Well, actually I have no idea. But I would guess it is because cancer cells spend a lot more time reproducing more cancer cells than they spend just sitting around trying to rest.

Any way, this whole 3 week cycle will repeat itself 6 times (Cycle 1 = Dec 7, 14, 21; Cycle 2 = Dec 28, Jan 4 & 11; Cycle 3 = Jan 18, 25, & Feb 1; Cycle 4 = Feb 8, 15, 22; Cycle 5 = March 1, 8, & 15; Cycle 6 = March 22, 29, & April 5). That assumes, of course, that each cycle goes off on schedule and does not have to be delayed.

Why would a cycle have to be delayed?

Well, these drugs are not as smart as we would like them to be. So they do a good job of interfering with cancer cells that are reproducing, but they also do a pretty good job of interfering with normal cells that are reproducing. What cells are those? Hair cells obviously - that is why most chemo patient get bald at some point or other. Blood cells also, which is usually the limiting factor. If too many of my white blood cells get knocked out, they may have to delay a cycle to allow them to recuperate a bit.

But for now I am assuming that I will complete the standard part of this chemo therapy regimen about the middle of April.

Now there is a third drug in this trial - Avastin. That is the experimental part that makes it a clinical trial.

All the women in the clinical trial will get an experimental drug, Bevacizuma, also known as Avastin, starting on the first day of the second cycle (for me, Monday Dec 28). Thereafter we will get that same drug on the first day of each 21 day cycle. However, while the regular chemotherapy ends with a last dose on April 5 (assuming no delays), the Avastin will continue on day 1 of 21 cycles, which is day 1 of cycles 2 - 22. This means after I quit getting the standard chemo on April 5, 2010, I will keep getting this experimental drug on the first day of each 21 day cycle for a total of 336 more days, which is nearly a year after I finish the standard chemotherapy. So I won't be a totally free woman again until sometime in the late spring or early summer of 2011. (which sounds like an awfully long time).

What is this Avastin? Avastin is a monoclonal antibody that is an "antiangiogenesis" agent. Antibodies are things that our own white blood cells produce in response to infections. When we get sick and afterward are Immune to that disease, that immunity is in part because our healthy white blood cells made antibodies that attack the same infection if they see it again. When we get vaccines and are protected by them, that is in part because our white blood cells make antibodies that attack the infection the vaccine was designed to protect us against.

So how does this work with cancer? Well normal natural antibodies that we produce for our protection are multiclonal - which is scientific talk for many versions ("multi" = many, "clonal" is like a family line - so multiclonal = many types, but monoclonal = 1 type only (mono = 1 or all alike).

Normal healthy antibodies that we produce attach to infections and mark them for destruction by our own immune systems.

This monoclonal antibody is targeted specifically to attach only to a protein produced by a cell (cytokine) called human vascular endothelial growth factor (VEGF). VEGF is produced by cells and leads to the development of new blood vessel formation (angiogenesis, "angio" = blood vessels and "genesis" means "In the beginning..." just like in the Bible, so angiogenesis is the beginning of blood vessels. Blood vessels bring food to the cells and take wastes away. So without the ability to form blood vessels new cells will starve while sitting there stewing in a cesspool of their own wastes.

Avastin is a totally new approach to cancer treatment that was approved by the FDA on the fast track a few years ago because it was proving so effective against colon and prostrate cancer, and it has also been approved for use with breast cancer although it is not clear that it is as effective there.

We don't know how or whether it will work for ovarian cancer, but it seems worth while to try it. And at the end of this research experiment, at worse doctor's will know a little more about how to treat cancer patients best. And at best I may get some benefit from having this additional line of attack on my cancer cells now.

Now in addition to the chemotherapy drugs, which are given to make things inconvenient for the cancer cells, I get other drugs that are intended to protect me from the chemotherapy drugs.

So since lots of people have allergic reactions to the Taxol, and I myself had a mild one the first time I went for chemo, before I get Taxol (my flower power drug) I get large doses of steroids (a cousin of the drugs athletes take to beef up faster and that lots of people with asthma take when they have a serious asthma attack) and of benadryl (an antihistamine, which many people take for allergies routinely) and sometimes of ativan. These drugs make me a bit manic, very loopy, and after the second dose of chemo last Monday left me amnesia (memory loss) from about 1 pm until about 8 pm that night. Wierd and spooky.

So while the chemotherapy drugs are not so bad, the medications i get first make me a menace on the highway. As a result my primary support need now is for someone to drive me to and from chemo every Monday. While I might do very well getting there on my own, I would clearly be in no condition to drive myself home, not because I am sick but because I am effectively drunk.

OK - a long discourse. Enough for now.

Again, thank you all for your support.


No comments:

Post a Comment