Adriamycin vs Epirubicin

jason222

Hi,

It seems that a lot of people are getting the AC regime compared to the EC.
From what I have read, basically adriamycin and epirubicin does the same thing, except Epirubicin is not as tough on the heart compared to adriamycin. Why do most oncologist still prefer the adriamycin compared to the epirubicin?

 My mum is currently undergoing the AC regime. Should I request the oncologist to go for EC instead to prevent any future problems on the heart due to adriamycin since both chemo does the same thing?

What's your opinion?

otter

Jason, I'm not triple-neg, but I saw that your question had not been answered yet. 

I think the decision to use Epirubicin vs. Adriamycin may depend on the country you are in.  Epirubicin seems to be used more often in Europe and Canada, while Adriamycin is used more often in the U.S.  I don't know why that's the case.  My oncologist first proposed that I would get Adriamycin/Cytoxan (I'm in the U.S.).  I was concerned about long-term heart problems, so I mentioned Epirubicin.  Instead, she suggested Taxotere/Cytoxan.

Maybe someone else can answer your question more specifically.  It's a good one.

otter 

HeatherBLocklear

Hi all,

It will probably turn out that Adriamycin is cheaper than Epirubicin. Is there any other reason for choosing certain treatment regimens over others in the USA?

Yours grumpily,

Annie

HeatherBLocklear

Yep. I was right. Although the abstract at the link below denies any advantage of epirubicin over adriamycin, it does include the info that epirubicin is 22 times more expensive than adriamycin. I'm not suprised at all.

Yours cynically,

Annie

http://jco.ascopubs.org/cgi/content/full/23/12/287

Here's another that claims no difference in efficacy between the two:

www.hindawi.com/GetPDF.aspx?doi=10.1155/S1357714X0000

jason222

 Thanks for the response.

So the only reason is cost?

And most oncologist open up the risk of getting heart disease for their patients just to save cost at the early stage? It seems like it may cause the patients to pay more as a consequences of heart disease due to adriamycin in the future.

 I am really considering asking the oncologist about epirubicin if thats the case if the effectiveness is the same.

What does the rest think? What would you do? 

otter

Here's the text of the article Annie found. 

It's actually a letter to the editor, written by Gerard Ventura in reference to an article (Bonneterre J, Roche H, Kerbrat P, et al: Long-term cardiac follow-up in relapse-free patients after six courses of fluorouracil, epirubicin, and cyclophosphamide, with either 50 or 100 mg of epirubicin, as adjuvant therapy for node-positive breast cancer: French Adjuvant Study Group. J Clin Oncol 22:3070-3079, 2004):

"Bonneterre at al. assert, 'the better cardiac toxicity profile of epirubicin, compared with doxorubicin.'  Clinical studies do not support this position.  In their study of six cycles of FEC-100, two (2.3%) of 85 patients experienced clinical congestive heart failure (CHF). A recent study of doxorubicin in 141 patients treated for lymphoma found only one case of CHF (0.7%). In the latter study, the median cumulative dose of doxorubicin was 300 mg/m^2, with virtually all patients having received > 250 mg/m^2. This is the same dosage found in doxorubicin-based adjuvant therapies of breast cancer, given at equitherapeutic dose-intensity to FEC-100.  Prior "equimolar" comparisons of the two anthracyclines favoring epirubicin are spurious because the drugs are dosed differently to obtain the maximum-tolerated dose.

The average wholesale cost of an equitherapeutic dose of epirubicin in the United States, where epirubicin is still under patent protection, is more than 22x the cost of doxorubicin. Outside of an industry-sponsored clinical trial, the substitution of epirubicin for doxorubicin has no compelling advantages for either safety or efficacy."

Bonneterre published a rebuttal to the criticisms from Ventura.  He said there had been studies documenting that epirubicin was as effective as, but less cardiotoxic than, doxorubicin, when used at equimolar doses.  However, he admitted that the effectiveness and safety of the two anthracyclines (epirubicin and doxorubicin) had never been compared head-to-head at their optimal therapeutic doses.

So, I guess the question is still open, at least here in the U.S. where the patent on epirubicin is still in effect.

otter 

[Added in edit:  I doubt our oncologists would care which drug we wanted them to use, as long as someone was willing to pay for it.  I'll bet the real problem is unwillingness of insurance companies in the U.S. to cover the significantly higher cost of epirubicin, if there isn't clear evidence that it is a better drug.  I don't know, though.  I do know some oncos in the U.S. who are concerned about cardiotoxicity are switching from Adriamycin to Taxotere, which is covered by many insurance companies.] 

HeatherBLocklear

I'll bet the real problem is unwillingness of insurance companies in the U.S. to cover the significantly higher cost of epirubicin, if there isn't clear evidence that it is a better drug.

My point exactly. Yet can't one argue that it might be considered a better drug if it does the same job on the cancer cells as adriamycin, but doesn't affect the heart as badly? Just a thought.

Addendum: In other countries, such as those in western Europe, a government-sponsored health plan picks up the cost for drugs et al. Therefore, no insurance companies (BTW, nobody ever blamed the doctors who are as captive of our miserable system as the patients themselves) can get involved, and the best treatment options are usually those selected.

Annie

drventura

Serves me right for googling my name. Oh well, here goes......   A mole is the atomic weight of a compound expressed in grams. A mole of adriamycin (also known as doxorubicin) is 543 grams. A mole of epirubicin is 579 grams (ie, quite similar; adriamycin has 96% the molar weight of epirubicin).

But no one doses chemotherapy in moles. For an average sized patient, a therapeutic dose of adriamycin is 90 milligrams; for the same patient, a therapeutic dose of epirubicin is 180 milligrams - twice as much.   So, does an "equimolar" dose of epirubicin have less chance of causing heart dysfunction than adriamycin? Yes. Does the equimolar dose of epirubicin, being only 50% of the effective therapeutic dose,  increase the chance that the cancer will recur? Yes. 

Rest assured, no one uses the 'equimolar" dose of epirubicin, they use the therapeutic dose. As mentioned above, no head to head comparison has been done, but data suggests that when each drug is dosed properly (ie, the therapeutic dose), the risk of heart toxicity is really the same. It's not an issue now as epirubicin is generic; but in the last few years when it was still under patent - and as per the american system, priced/reimbursed at whatever price the company wished - the cardiac "safety" issue was extensively marketed, with the "equimolar" qualification buried in the fine print. So it was not an issue of using a less safe drug because it was cheaper; it was an issue of using an equivalent drug costing a patient 22 times as much.

While under patent, the epirubicin manufacturer financially supported hospitals using the drug in clinical trials, as do all drug companies and research hospitals. FWIW, now that those trials are over, most large centers (at least in the USA) have gone back to adriamycin when this class of drug is used. If cardiac function is a concern, the logical option is as your mother's oncologist suggested- foregoing both of these drugs and substituting taxotere instead ( a non-anthracycline drug).  

Regarding cynicism, may I offer the concluding lines of the Desiderata: "With all it's sham, drudgery and broken dreams, it is still a beautiful world. Strive to be happy."

best regards,    gv

HeatherBLocklear

GV et al.,

All I can answer in regard to American pharmaceutical and insurance companies is Lasciate ogne speranza, voi ch'intrate.

Regards back,

Annie Camel Duodenum

Edited to add: Do people actually Google their own names? Egads!

otter

Dr. Ventura, I appreciate your first-hand contribution to our discussion.  I'm also glad you Googled your own name, and found our mention of your letter here.  (Yes, Annie, it's interesting to Google your own name occasionally, just to see what's out there.)

My oncologist (at an NCI comprehensive cancer center in the southeastern U.S.) was skeptical when I asked her about epirubicin as a less-cardiotoxic alternative to doxorubicin.  We didn't spend much time on it, but I had the impression that she really didn't think epirubicin was less cardiotoxic--or at least, the difference was not significant.  Your post explains her skepticism.  She did not hesitate to consider, and agree to, Taxotere instead of doxorubicin, though.

Dang it, Annie, you keep giving me stuff I have to translate.  "Lasciate ogne speranza, voi ch'intrate" ...?  Thank you, Google.  I actually had to read Dante's Inferno (a small part of it) for a course I taught 10 years ago.  I was the "science" half of a "science & humanities" teaching team in a course patterned after "The Ascent of Man."  Needless to say, I did a lot better with Darwin than I did with Dante.

Oops. Gotta go.  Thanks again, Dr. Ventura, for dropping by here and giving us a logical explanation.

otter