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Friday, August 31, 2012

What is R-CHOP?

R-CHOP is one of the most commonly used regimens out there for lymphoma.  I wanted to briefly write about what the different ingredients are - how they work - what patients experience - etc.  R-CHOP actually is a cocktail of 5 different drugs.  Each letter represents one of the drugs.  Here goes...

R=Rituxan.  Rituxan is an antibody.  You make antibodies to fight colds, flu, e.coli, etc.  Instead of a naturally occurring antibody, this one is "engineered" to bind to the outside of a lymphoma/leukemia cell and alert the immune system to go after it.  See my other post "Building a better CD20 antibody."  People can often have "infusion reactions" with the first dose (chills, shaking, shortness of breath, rash, etc).  If you actually measure "b-cells" in the blood while administering the antibody, you can see them disappear from the blood during the infusion.  As those b-cells go away they release little hormones that cause the symptoms.  Often the symptoms do not recur with subsequent doses as the B cells are gone.  Overall, most people tolerate the drug extremely well and are not even aware they are getting a very effective anti-cancer treatment.  Those patients with side effects can often be managed by extra tylenol, benadryl, steroids, etc.

C=Cyclophosphamide.  This is an old school chemotherapy that has been around for quite a few years. It binds to DNA in the nucleus of the cancer cell and prevents effective replication of the cells genome. Those cells that divide more rapidly are more sensitive to the treatment.  Therefore cancer cells and normal bone marrow are most affected.  It lowers healthy blood cells as well as bad ones.  Fortunately the good guys recover more quickly.  It can also cause nausea but our nausea medications are so good, that is rarely a problem.  There can be bleeding in the bladder but I have given a ton of cytoxan and I've never seen it as a problem.

H=Hydroxyrubicin (which we call Adriamycin).  Some call this drug "Big Red" as it has a pinkish / red color and can make your urine discolored for 24-48 hours.  When you talk about R-CVP the only difference is that this drug is missing.  Hydroxyrubicin "intercalates" or "slips between" the base pairs of DNA.  DNA is a coiled structure.  In order to copy it, you need to unzip the two strands.  This creates a lot of "torque" or "strain" that needs to be released.   It is like a hair dryer cord that gets turned around and bound up in knots.  To relieve the strain there are enzymes called "topoisomerases" which nick the DNA so it can spin around and release the tension and then get re-attached.  Adriamycin prevents that and results in "double stranded DNA breaks."  These are harder for the cancer cell to repair than single stranded breaks.  The side effect profile is notable for hair loss and low blood counts.  The fear of adriamycin is that it can weaken the heart muscle.  You can usually get away with 6-8 doses of the drug, but after that point the risk of heart damage really goes up.  In uncommon situations, it can cause some permanent injury to your bone marrow stem cells and in extremely rare circumstances even cause a second cancer.... aargh!

O=Oncovin (which we call vincristine).  Vincristine is what we call a "microtubule inhibitor."  Other microtuble drugs include vinblastine, taxol, taxotere, eribulin, etc.  Microtubules are like the cellular "skeleton."  It helps hold all the pieces of the cell where they want to be.  When cells need to separate their chromosomes into daughter cells they use microtubules to help pull them apart to the opposite sides of the cell.  They chew up one end and add pieces to the other which creates a sense of "movement."  Vincristine freezes that process and cells don't like that.  If they stay frozen too long they trigger cell death.  It causes some numbness in finger tips and toes and possibly constipation.

P=Prednisone (yes the good old fashioned steroid).  You are probably familiar with prednisone for things like rashes or arthritis etc.  We use it to lower the immune system.  Lymphoma is simply a cancer of the immune system.  I have had occasion to "cool off" a patient while trying to collect additional tests.  I can sometimes give them a slug of steroids while I am waiting and see their lymph nodes shrink.

Sometimes when we tell patients about potential side effects, I get the impression the cure sounds a lot worse than the disease.  Doc's probably practice defensive medicine more than we realize.  If we tell you everything that can go wrong, then we feel we are less likely to get sued if something bad happens.  Unfortunately you see some patients go through the side effect list and freak out - understandably.

I often say that chemotherapy is a lot like a "stereo dial."  We can turn it up to 10 (unbearable) or down to 1 (was that chemo you just gave me?).  R-CHOP is somewhere between a 4-6.  Nausea isn't often much of an issue.  Fatigue is considerable.  Many people can work while getting chemo, but some folks are better off taking the time off of work (if they can).  Somehow the hair loss makes you feel like a cancer patient.  After you have had one dose of chemo (a cycle is every three weeks you get one dose) I tell patients that they have seen 80% of the side effects.  Yes there is some degree to which things are cumulative, but for the most part you have seen the side effects.

Hopefully that helps.  In another post, I will talk about how I approach DLBCL and when I choose alternatives.