day 38 that’s how I know the chemo is working

This Wednesday was only my fourth taxol, but I am beginning to feel the side effects. It’s a little earlier than anticipated, and its nothing major. And of course, everyone’s experience is a little different.

Mostly I have the feeling of cold feet, but they are not cold. I have checked, and even asked my wife to check… But for much of the day I feel that my feet are cold, even when I weak socks and shoes and am walking briskly from meeting to meeting. My hands are also getting some odd feelings – mostly a smooth sensation if I rub them together, or when I touch something. They are also sometimes cold, which explains the rubbing together. 

Then there is the flushing. The first three taxol’s gave me a decent day and half of thirst and flushed cheeks, and I was thinking it was the steroids that I get just before the chemo itself. But this week the steroid dose was dropped to a much lower level, and my flushing is stronger. This morning in the shower I had the dial way off where I usually have it and it still felt uncomfortably hot. Mostly this is in my upper body and face, as the side effects list says. I don’t have a fever and carry a thermometer with me all day, and check probably more often than necessary. I wonder whether this is what hot flashes feel like, and whether that may just be a little too far into the land of pink for a guy 😉

Oh, and I don’t need to shave any more, which saves time in the morning. My hair, such as it is, and it hasn’t been much for quite a few years, is still hanging in there.

The common thing is that feelings that usually mean something, at the moment mean something else. The cold feet don’t mean that I need to put warmer socks on. And the hot feeling doesn’t mean I have a fever. I just feel odd – cold on the bottom and hot on top, and mildly confused all around.

Then yesterday was also the first day that I missed a meeting because I didn’t feel well enough to go. I had to sit at my desk for half an hour with my eyes closed to fight back a headache that was building in the morning. I was drinking plenty of water, and staying away from too much coffee, but it slowed me down for a bit. I was able to get through it and keep the rest of my appointments after lunch – some chicken noodle soup helped revive me. 

The good news is that this all means the drug is in my body and active. While it doesn’t guarantee that the tumor will respond, it does mean we are giving it a shot. Side effects are really just the drug acting on normal systems in your body, but it does that in the same way as it affects the tumor. I wrote on day 22 about how taxol works, by affecting the cytoskeleton of cells, specifically the microtubules that cells used to divide, but also use for lots of other important tasks. When some of these get hit, you get side effects. 

One of the key problems in treating cancer is that the cancer cells are very similar to your normal cells – after all cancer cells are your bodies normal cells, gone bad. When you think about a virus or a bacterial infection that’s more like an invasion by another organism, and in treating these invaders you can focus on biological processes that are different. For example, many bacteria have a tough outer shell called a cell wall, which they make out of sugars. We don’t have anything like that in our bodies, and many antibiotics prevent the formation of this cell wall. That’s a great drug, because it kills the bacteria but is irrelevant to the human cell. For cancer we don’t have that option. 

For cancer we have two basic approaches: try and inhibit something that the cancer absolutely needs to do, but that the body can do without for a bit, or target mutations that are in the cancer but not in the body. The former is the traditional chemo approach. With taxol we are trying to shut off cell division in my body, which will kill the cancer, but which my normal cells can weather. That’s because my normal cells, even the ones that usually divide, get the message to stop, and do so in a well behaved manner. They go into a stasis mode that they can recover from. The cancer cells, which are out of control, don’t get that message and can’t put the brakes on, and so many of them end up dying. But the loss of cell division does cause the problems commonly encountered, such as hair loss and loss of immune function. Most established cancer therapies focus on cell division in one way or another.

The other approach is much more elegant, and the coming way of the personalized, molecular or genomic medicine you may have read about. The idea is that if the cancer has a mutation it now has something that distinguishes it from the rest of the body, a bit like the cell wall of an invading bacteria. Herceptin and Her-2 is one of the earliest example, although this relies more on the fact that the Her-2 is present in some breast cancers at a higher levels, not that it is mutated there. Similarly cetuximab and EGFR and gleevec and tyrosine kinase receptors. A better example of the new approach is the B-raf gene and vemurafanib, where the drug hits mainly the mutated form of B-raf V600E (http://en.wikipedia.org/wiki/BRAF_(gene)). This drug has remarkable efficacy on the cancer, and represents the approach of the future. These drugs will still have side effects, because they will still have some impact on normal cells, but the therapeutic window promises to be much bigger – meaning that you get more therapeutic effect and less side effects.

Anyway, I am happy that the tried and true taxol is doing its thing. I know there is much more to come, but I feel that we are really hitting it now. 

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