Drugs 4: Dacarbazine

Out of all the chemotherapy drugs I am getting, dacarbazine is the one I really loathe.  The reason for this is because of the pain that it causes.   At my first chemotherapy session, I already had a bizarre arm pain from this drug.  They put hot compresses on my arm, but that only helped minimally.  It is because of dacarbazine that I eventually had to get the line and then the port.  Dacarbazine is also known as DTIC.


Truthfully, I couldn't find many interesting tidbits or factoids about dacarbazine while surfing the web.  I'm sure some are out there, but they were not obvious to me.  


Doing a quick google image search, I found the structure of dacarbazine.  It appears to be a (relatively) simple molecule.

So, how does it work?

Per Lexi-Comp:

Alkylating agent which appears to form methylcarbonium ions that attack nucleophilic groups in DNA; cross-links strands of DNA resulting in the inhibition of DNA, RNA, and protein synthesis, the exact mechanism of action is still unclear.

In other words, much like some of the others, it inserts itself into the cancer cells' DNA, and prevents "normal" replication.  I put normal in quotation marks, since cancer cells obviously do not have a normal replication process.  

What side effects does it cause?
Well, as noted above, the side effects for this drug starts and ends with arm pain, in my case that left arm.  It would seem that the package insert does not agree with me.  Astonishingly, it does not even mention infusion pain, although it does discuss extravasation.  Lexi, however, does note that > 10% of patients will have pain on infusion, and suggests the drug be given over 30-60 minutes as rapid infusion can cause severe venous irritation.


The other side effects noted include GI side effects, which mostly include nausea and vomiting.  Curiously, the package insert suggests a strategy of having patients not eat for 4-6 hours prior to infusion to combat diarrhea.  Since so many other parts of my treatment are constipating, I guess this tends to even those out since (thankfully), I haven't had too much burden with either problem.  I can say from my own experience that the only thing worse than being really full during chemotherapy session is being very hungry.  Dacarbazine obviously also causes leukopenia, thrombocytopenia, and myelosuppression. I have not noticed thrombocytopenia.


Also, like others in this regimen, dacarbazine displays biphasic elimination, with an initial half-life of 20 minutes and a terminal half-life of 5 hours.  In other words, this is mostly gone after about a day.  It is eliminated 30-50% unchanged in the urine, and the other half or two-thirds is extensively metabolized by  1A2 and 2E1, which are less common P450 isozymes.  It is minimally protein bound, and has a volume of distribution not much more than the total body water, in other words, fairly small.


As a result of being a 1A2 and 2E1 substrate, there are some potential drug interactions, but none that affect me, or (I'd venture) most people on the ABVD regimen.


The typical dacarbazine dose is 375 mg/m2.  So, given my own math of a BSA of ~ 2.26m2, that would be about 847mg, and my dose is 840mg.   As a result of all the pain I had, I now get this in a bag that is approximately somewhere between 500mL and 1 liter, and so even with the port, this drug feels like it takes forever to infuse.  Dacarbazine is colorless.


What other cancers is dacarbazine used in?
It is used in malignant melanoma and Hodgkin's, obviously, it is also being studied in treatment of soft-tissue sarcomas, islet cell tumors, pheochromocytoma, and medullary carcinoma of the thyroid, per Lexi.


What else can I say about dacarbazine?
Not much.  Just a boring, painful drug. Doing this post doesn't make me like it any more, that's for sure. Package insert is here.  Chemocare's website is here.