Cancer Drug Shortage Is Costing Lives

MD Anderson Cancer Center
Date: 04/04/2011

 

Lisa Garvin: Welcome to Cancer Newsline, a weekly podcast series from the University of Texas M. D. Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today, we have a very serious subject Cancer Drug Shortages and with us to address that is the Chair of the Leukemia Department here at M. D. Anderson, Dr. Hagop Kantarijian. Welcome Dr. Kantarijian!

Dr. Kantarijian: Thank you for inviting me.

Lisa Garvin: And you've been kind of on your soapbox lately and particularly the drug that concerns you most is cytarabine also known as ARA-C. Tell us about that.

Dr. Kantarijian: The story of cytarabine is a very sad one and it's almost a national tragedy that nobody is paying attention to. To give you a little background on the drug, in the United States there are about ten thousand cases of acute myeloid leukemia every year, so that's about 20 to 30 cases on a daily basis. In these patients, if we give them the correct treatment on day one, the cure rate is 40 to 50% and the correct treatment is with cytarabine, and in simple terms, if they can get cytarabine, their cure rate is 40 to 50%. If they do not get cytarabine, the cure rate is 0%. Nobody is cured without cytarabine and there's no replacement to that drug. So we are in a nightmarish situation where we get calls from all over the United States of oncologists asking me about a patient who has AML and the fact that there is no cytarabine and what should they do and what I tell them is there's no alternative. You have to call, you have to make noise, you have to call your Congressman and Senator and ask why is it allowed in the United States today to have a patient with acute myeloid leukemia who is not able to have cytarabine, which is an inexpensive and generic drug. I simply do not understand the deafening silence behind this major problem, which may be killing US citizens on a daily basis.

Lisa Garvin: And what seems to be the problem? I mean is there, I mean there are several things like manufacturing delays, lack of proper ingredients, what is the issue?

Dr. Kantarijian: I do not understand what the issue is and whatever the excuses are it amazes me that they are applicable only to the United States. Why is it that those problems are not happening anywhere but in the United States? So today a person is less unfortunate if he is diagnosed to have acute myeloid leukemia in a third world country, like my native Lebanon, because they have access to ARA-C; there have been no shortages of the drug in anywhere in the world, except in the United States. So we need an investigation as to why these drug shortages started happening recently, probably since 2008. Why the number of drugs in shortages is increasing on a continuous basis and why nobody is paying attention to this? And notice that all these drug shortages are in generic drugs, not in patented drugs, not in drugs that are expensive. So whenever you have an expensive drug, it seems that everybody can manufacture it and there's no shortages, but when you have a generic drug, where the profit margin is short, we're seeing an increasing problem of these shortages but only in the United States, nowhere else in the world. So we need to know what is happening in the United States and we need to call our leaders to ask them to find a quick solution to a problem that may be killing US citizens.

Lisa Garvin: I would assume this would give rise to a black market for shortages of drugs, have you seen that?

Dr. Kantarijian: I do not know about black market, I heard as of yesterday that there is apparently a gray market for drug shortages. So apparently, there's a group of people who can get you those drugs at 10 to 20% of the accepted price in a gray market. So I do not know how much this is contributing to the problem and why should there be a profit issue with a drug that can save the lives of patients.

Lisa Garvin: I understand and I saw a recent news report in which you were being interviewed and you said that M. D. Anderson had a sufficient supply at least for now. Is that true?

Dr. Kantarijian: We are fortunate to be in the Leukemia Department at M. D. Anderson. This is the largest leukemia department in the world and because we have 25 leukemia physicians and we see over 1600 to 1800 new leukemias a year, we are fortunate to have an institution that has the financial capacity to predict and to prevent these shortages, but even in the medical center, which is the largest medical center in the world, I get calls on a daily basis about the shortages of drugs, in particular cytarabine. Now those drug shortages may be less critical for other generics where there are replacements, similar replacements, but there is no substitute to cytarabine and even for the other drugs, the oncologists are starting to concoct combinations that we've never used before assuming that the substituted drug will have the same efficacy and toxicity profile as the replaced the drug and that's not the case so we're going into our uncharted territories where we are inventing combinations of regimens for curative diseases like lymphoma and Hodgkin's disease with replacement drugs that we have very little experience with.

Lisa Garvin: And you're doing that outside of the clinical trial process?

Dr. Kantarijian: And this is being done outside the clinical trial process, this is simply patient care. It has nothing with research or clinical trials.

Lisa Garvin: Now are hospitals allowed to do a little horse trading, like say, you know, Memorial Hermann down the street could they say, could they purchase from each other? I mean is that allowed and is that happening?

Dr. Kantarijian: I think, I think we need to help each other and I think part of this may be happening. But again, as the largest leukemia group, we have our responsibility and duty towards the leukemia patients who come to us. This is a unique disease where if we're the largest leukemia group and we have a bulk of leukemia patients, we have to make sure that every patient referred to us will get the drug and not be short of it.

Lisa Garvin: Let's talk a little bit about AML. It's an acute form of leukemia, let's talk about that disease.

Dr. Kantarijian: So as I mentioned acute myeloid leukemia is a disease that affects about ten thousand individuals. It usually affects in older populations so the average age is about 65 years. What we do is treat them with combinations of cytarabine. So cytarabine was FDA approved in the 70's and since it was introduced consistently to the treatment of acute myeloid leukemia, the cure rate has gone from 0% to 40 to 50%. For that cure rate to happen, you have to have the right treatment on day one and you have to give several courses of chemotherapy, probably up to four to six. So at any point in time, particularly during the induction, if you have a cytarabine shortage, that could affect the cure rate of these patients significantly.

Lisa Garvin: Because it's a fast progressing disease is it not?

Dr. Kantarijian: That's correct. So if you do not treat a person with acute myeloid leukemia, they can die within a month to two months.

Lisa Garvin: And let's talk about some other major cancer drugs that are also in shortage. Doxorubicin also known as Adriamycin, which is a very popular drug and the platinum based drugs, is that causing an issue here as well?

Dr. Kantarijian: It is also a big issue. There are shortages of anthracycline, of nitrogen mustard, of vincristine, of Decadron and other steroids, of the etoposide and the platinum analogs. Now with all of these, there are substitutes. Now I do not call them reasonable substitutes because it's never reasonable to substitute a drug for another when there is no experience with that combination. Many of these substitutes are brand name drugs as opposed to generic drugs. So we're creating a situation where the cost of care increases significantly with the generic drug shortages and we're using regimens that we have very little experience with. So we're increasing the cost and potentially reducing the potential cure rate and increasing the toxicity to these patients when these generic drugs are in shortages.

Lisa Garvin: What is it about cytarabine? It's been around a long time, it seems like the work horse, you know, of leukemia drugs, what's so special about it?

Dr. Kantarijian: It is correct. As with a lot of cancer discoveries, cytarabine is a cancer discovery that happened in the late 60's early 70's. It's the one drug that has cured the most of patients with acute myeloid leukemia. We have looked at many chemical cousins of the drug and none of them is even close to the efficacy of cytarabine as a potentially curative treatment of acute myeloid leukemia. So when you look at the cytarabine analogs, there are drugs like fazarabine, capecitabine, sapacitabine, decitabine, azacitidine, none of these drugs is even close to being as effective as cytarabine in curing acute myeloid leukemia.

Lisa Garvin: Because I know you have dozens of clinical trials going on and a lot of your patients are in protocols, so nothing even has come close to cytarabine.

Dr. Kantarijian: For acute myeloid leukemia, nothing has come close to cytarabine and there's unfortunately no substitute to cytarabine and that's why it is a national crisis and it is a tragedy that in 2011 in the United States we have this kind of a crisis.

Lisa Garvin: What would happen to a patient, because I think you said it affects the rural areas and particularly in the smaller cities. What? Should patients be asking questions of their doctor? Say they are diagnosed with AML, should they be asking whether this drug is available at their place of choice?

Dr. Kantarijian: They should and they should move very quickly to a place where the drug is available within a couple of days, and if not, they should call their Congress people and their Senators and their oncologist has to help them do that so that they create enough momentum and national awareness about this tragedy so that somebody does something about this problem.

Lisa Garvin: How many AML patients are diagnosed every year?

Dr. Kantarijian: Every year we have about ten thousand new cases of acute myeloid leukemia in the United States.

Lisa Garvin: So in the scheme of things it would be considered a rare cancer, it seems it would be hard to build awareness of the cytarabine shortage. Do you find that to be a challenge?

Dr. Kantarijian: That's correct. I think the problem with cytarabine is two-fold: one that the leukemia we're talking about is a rare tumor and so you do not have a body that advocates for it. And second, that ARA-C is generic and so there is no power house or financial incentive behind advocating for the drug. So, for example, in breast cancer when there was the issue of bevacizumab being withdrawn by the FDA because the, the trials did not show potential efficacy, there were at least six articles in different newspapers alluding to the fact that the drug is useful and should not be withdrawn. With cytarabine, I cannot even get one editorial in one newspaper to try to bring this issue to national attention. And I think part of the problem is the fact that cytarabine is generic and there is no profit margin and there are no advocacy groups behind it.

Lisa Garvin: It seems like you have become the champion though. What will you continue to do to address this shortage?

Dr. Kantarijian: I think as leukemia physicians we have a moral obligation to continue to bring this issue to the national attention until this problem is solved in the United States. It's our moral obligation towards our US citizens to do this to try to save these people. Every day there are 20 to 30 people who can be affected. Now when you have few people die in Afghanistan or in Pakistan through the war processes, this is immediately front page in the newspapers. When it is leukemia patients who can't have access to ARA-C, nobody is talking about it.

Lisa Garvin: Well it sounds like you've got your work cut out for you Dr. Kantarijian and I wish you luck.

Dr. Kantarijian: Thank you for giving me the opportunity to present the case.

Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline, contact Ask M. D. Anderson at 1877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.