Drugs 2: Bleomycin

This will be the second installment of the look into my new drugs.  Today's drug is bleomycin (former trade name Blenoxane, although it is long since generic).  It is the "B" of ABVD.  Bleomycin is a drug that initially scared me because it is known for its lung toxicity.  In fact, they didn't even give it to Lance Armstrong, opting for another regimen.   Not that I need my lungs to quite the same capacity that he does, but I still want to preserve what I can as best as possible.  Which reminds me, there is definitely some sarcasm scattered throughout this particular update.  It is my attempt at humor, not anger.

Bleomycin isn't colored like the doxorubicin is.  It is clear liquid that I get as an IV from a syringe.  It looks like cold water being pushed.  Why cold?  I don't know.  That's just what I always imagine.  It doesn't feel that cool.  The nurses like to push it slowly, but without the color as an indicator, it is difficult to get a feel for what rate it is actually being pushed.  Bleomycin is also a vesicant and an irritant.  In other words, it can hurt when given. 

My dose each chemotherapy session is 22.401 units.   1 unit = 1mg.  This is about 0.25 units/kg.  This puts my total cumulative dose after 12 chemotherapy sessions at 268.812 units.  The maximum cumulative lifetime dose is 400 units.  The reason for this is pulmonary fibrosis.  


According to the package insert's boxed warning:

Pulmonary fibrosis is the most severe toxicity associated with BLENOXANE. The most frequent presentation is pneumonitis occasionally progressing to pulmonary fibrosis. Its occurrence is higher in elderly patients and in those receiving greater than 400 units total dose, but pulmonary toxicity has been observed in young patients and those treated with low doses. 

This is obviously very confidence-inspiring.   Bleomycin has a variety of side effects, but, lung toxicity is  my primary concern.  According to the same package insert, it occurs in about 10% of treated patients.  This toxicity may be enhanced when used with G-CSF.   (Sidenote:  G-CSF is a drug that stimulates neutrophils, a type of white blood cell.  I am not currently on it).   The earliest symptom is dyspnea, which is fabulous for me, since I already have shortness of breath from having enlarged lymph nodes all over my chest.  Basically, bleomycin scars up the alveoli in the lungs.  Later, an excess concentration of oxygen can cause an oxygen toxicity and further problems.  Too much oxygen is not typically an issue here in Colorado, although it would be an issue if I were to have general anesthesia during a future surgery, and this is what precludes me from ever going SCUBA diving.  After I get done with this drug, I just cannot wait to have 20 days of radiation on my chest.


Unlike the doxorubicin, where it was somewhat more difficult to predict side effects directly due to the drug's use in regimens only, bleomycin is used as a single agent, and so other side effects can be more directly attributed.  Another boxed warning indicates "a severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing has been reported in approximately 1% of lymphoma patients."  Beyond that, it can cause "erythema, rash, striae, vesiculation, hyperpigmentation, and tenderness of the skin."  It can also cause Raynaud's phenomenon, as well as hair loss and the mucositis.  So, once past the pulmonary toxicity, there aren't too many other side effects, like some of the other drugs.  It is considered to have very low emetogenic potential.


One last interesting side effect it can cause is dermatographism.   This is an especially interesting side effect (definitely click the link!), because I already HAD it prior to treatment.  According to my oncologist, it occasionally occurs in Hodgkin's Lymphoma.  She demonstrated this to Sarah with a nice line across my back, just for her.  Actually, I haven't checked recently to see if this is still an issue I have, although it was another reason for the t-shirts.


How does it work?   Bleomycin is an antibiotic, per wikipedia.  (We do NOT use it as one, incidentally).  As someone involved in the world of infectious diseases, it is often easier for me to think of cancer as an infection (it is one of sorts), and so the mechanisms make more sense.  Bleomycin inhibits the synthesis of DNA by binding to it, reacting with oxygen, and causing single and double stranded breaks.  Without DNA for reproduction, rapidly dividing cancer cells can't, well, rapidly divide.  However, unlike most commonly used antibiotics, it isn't perfectly specific for its target (cancer cells), and can hit other rapidly dividing cells, such as hair, nails, and those of the GI tract, which lead to the side effects that nearly all chemotherapy patients experience.


Pharmacokinetics:  Bleomycin is widely distributed although it does not cross the blood-brain barrier.  The highest concentrations of bleomycin can be found in the highest concentrations in skin, kidney, lung, heart tissues.  Bleomycin has biphasic elimination (which means the concentration-time curve, when logarithmically transformed, basically has a kink).  The reason for this is that the drug is first metabolized, then excreted via kidneys.  The enzyme responsible for metabolism is a cytosolic cysteine proteinase enzyme, which is apparently now named bleomycin hydrolase.  This was new to me and per the package insert.  So, for people with normal kidney function, the initial half life is about 90 minutes, and the terminal is about 9 hours, hence the kink in the graph.  Therefore, if I get this mid-day on a Monday, it is nearly all gone by mid-day on Wednesday.


What other cancers is Bleomycin used for?
Well, obviously testicular cancer, since it was an option for Lance Armstrong.  Beyond that, per Lexi-Comp, it is used for quamous cell carcinomas, melanomas, sarcomas, Hodgkin's lymphoma, and non-Hodgkin's lymphoma, and it is also used as a sclerosing agent for malignant pleural effusion.  


What else to say about bleomycin?   I'm sort of afraid of it, and it is going to be difficult to monitor for toxicity due to the nature of my particular disease location(s).  Not tons of info from Wikipedia.  The package insert is found here.  Chemocare has a nice website as well.