anemia drugs

[bety]

Please read article in today’s nytimes : Studies show anemia drugs may harm cancer patients, by andrew pollack. You may want to discuss the article with your hematologist.

[Carl]

HERE IS THE ARTICLE FROM THE TIMES:

Studies Show Anemia Drugs May Harm Cancer Patients

By ANDREW POLLACK
Published: February 27, 2007

New studies are raising questions about whether drugs that have been used by millions of cancer patients might actually be harming them.

The drugs, sold by Amgen, Roche and Johnson & Johnson, are used to treat anemia caused by chemotherapy and meant to reduce the need for blood transfusions and give patients more energy. But the new results suggest that the drugs may make the cancer itself worse.

In the studies, the drugs have generally been used in ways not approved on the labels. And the companies say that, when used according to instructions, the drugs have a long history of safety.

In a statement yesterday, Amgen said it strongly believed its drugs were “safe and effective medicines when used in approved populations consistent with label dosing recommendations.”

Nevertheless, some cancer specialists and securities analysts say the new information may make doctors more cautious in using the drugs, which have combined sales for the three companies exceeding $11 billion and have been heavily promoted through efforts that include television commercials.

“These are drugs that were presumed to be entirely safe, given for supportive care and to improve quality of life,” not to actually treat cancer, said Dr. Eric Winer, director of breast oncology center at the Dana-Farber Cancer Institute in Boston. “So any concern that they could shorten someone’s life are taken quite seriously.”

The Food and Drug Administration is planning to convene an advisory committee meeting to review the products, Dr. Richard Pazdur, the agency’s director for cancer drugs, said in an e-mail message last week alerting cancer doctors to the new findings.

All the drugs are versions of erythropoietin, or Epo, a substance made by the human kidney that increases levels of hemoglobin, the oxygen-carrying component of red blood cells.

Amgen makes Aranesp, with sales of $4.1 billion last year, as well as Epogen, which had sales of $2.5 billion, although Epogen is supposed to be used only to treat anemia in kidney dialysis patients.

Under license from Amgen, Johnson & Johnson sells Procrit in the United States and Eprex abroad, with combined sales last year of $3.2 billion.

Roche’s drugs NeoRecormon and Epogin, now sold only outside the United States, had sales last year of $1.8 billion. But Roche is hoping to enter the American market with a new drug called Cera.

Amgen has the most to lose from any setback because it relies more heavily on the Epo drugs, which account for nearly half its revenue. Amgen’s stock touched above $75 briefly in late January, before word of the negative studies began emerging. The shares closed yesterday at $66.20, down 3 cents.

The new doubts about cancer safety add to those raised recently regarding the drugs’ other major use — to treat anemia caused by kidney disease. A study published in The New England Journal of Medicine in November found that patients treated aggressively with Procrit had a higher risk of heart problems or death than those treated less aggressively.

The run of bad news for cancer treatment started in late January when Amgen announced that in one of its clinical trials, patients getting Aranesp were more likely to die than those getting placebo. The trial was testing the drug in patients whose anemia was caused by the cancer itself, not by chemotherapy.

On Feb. 16, the Cancer Letter, an influential Washington newsletter, reported that a Danish study in patients with head and neck cancer had been stopped early because the cancer seemed to recur more in patients being treated with Aranesp.

Last week, The Journal of Clinical Oncology published a paper online describing a small Canadian trial in lung cancer patients that had been stopped early because those getting Eprex were dying sooner.

And on Friday, Roche said it was suspending patient enrollment in a lung cancer trial comparing its Cera against Amgen’s Aranesp because of apparently greater than expected number of deaths in at least some of the arms of the trial.

It is not known why the drugs cause problems, if they do. It is known that raising hemoglobin levels too high increases the risk of blood clots. And most of these new trials did aim to increase hemoglobin above the levels recommended in the drugs’ labels, though that was not the case with Amgen’s own trial.

But there is some evidence that clots were not the problem in these trials. Rather, some experts say, Epo may spur tumor growth. Some studies suggest that certain tumor cells, such as those in head and neck cancer, have proteins on their surface that bind to Epo. When that happens it sets off a cascade of reactions spurring growth.

“I think there’s enough biologic plausibility to the argument that they can serve as a growth factor for the cancer cell,” said Dr. Jennifer R. Grandis, a professor at the University of Pittsburgh who has done studies of the matter. She said the head and neck cancer practice at her institution does not routinely use Epo and that she would not want it herself.

But Dr. David P. Steensma at the Mayo Clinic, who has reviewed studies of Epo safety, said the existence of Epo receptors on tumors had not been proved because the studies have been flawed. He said that there have been previous studies of the drugs that suggested they actually had a positive effect on survival.

A combined analysis of 57 trials concluded the impact of the drugs on survival was uncertain.

Dr. Steensma said he was still comfortable using the drugs to correct severe anemia, but added, “I think we need to be real careful about going beyond that.”

Concerns about the safety of the drugs for cancer were first raised in 2003 by two studies that showed patients getting Epo had worse outcomes. But some experts said those studies were flawed and not convincing.

[patti]

[QUOTE]Originally posted by Carl:
[QB]
The trial was testing the drug in patients whose anemia was caused by the cancer itself, not by chemotherapy.

“I think there’s enough biologic plausibility to the argument that they can serve as a growth factor for the cancer cell,” [QB]

These are two very important statements. MDS would fall into this class of anemia caused by cancer itself.

Mom and I talked to her nurse practioner about this several years ago. At that time neither procrit nor aranesp were working (she was on them for 9 months) and we both said we felt it was only progressing mom’s disease because if it wasn’t spurring out red cells it was probably growing leukemic cells. While the NP agreed with us and we stopped it the doctor did not agree that would be happening. Even if it had worked for mom, it is a growth factor and logic says it will cause the good and the bad to grow (especially in blood cancers).

The bummer is, while these didn’t work for mom, they do work for a lot of people. So what’s someone to choose, their disease getting worse faster, death by short order, or transfusion dependency for who knows how many years? Not a very pretty option we have, huh?

Culpability on the part of the drug company? Sure looks like it to me.

Patti

[eve]

when my dad was on procrit at the very start of his disease (or at least we thought that was the start of the mds – it could have gone undetected for many years prior)it did little to help him – his hemodoc at that time said to get off the procrit because if it isn’t helping it might very well be hurting – once dad started the vidaza the procrit seemed to work – i guess it was the combination of the two

who knows

eve

[Neil]

The Times article referred to cancer patients who had anemia caused by chemotherapy.
Most MDS patients do not have anemia as a result of chemo. Those with secondary MDS and perhaps those who were treated for AML and transformed back to MDS could be exceptions.
BUT there are many of us who have been successfully treated with Procrit, Epogen and Aranesp. I was on Procrit for 32 months and now on Aranesp for 7 months. They both have been very effective in raising my red cell counts and have made a very big difference in my quality of life.
There have been instances where some patients received higher than recommended dosages. The manufacturers are very clear in their warnings that blood clots may occur if the warnings are ignored.
There have been many cancer patients who were successfully treated with EPO. Lance Armstrong is a classic example.
I prefer to leave my future in the hands of docs that have considerable experience with the treatment of MDS. There are major differences in the treatment of those with MDS compared to those with anemia related cancer treatment. Most MDS patients with low red counts have them as a result of the disease not from chemo.
My hemo and my internist have been keeping a very active level of interest in my overall health beyond the effects of MDS, in order to make certain the MDS does not trigger some other problems.

[patti]

Neil,

I read that differently then you did. It says that the anemia is caused by the cancer itself, NOT chemotherapy. What that says to me is that cancers like MDS (to be technical it’s like a blood cancer) or leukemia caused anemias fall into this category. Not arguing, just wanted to clarify.

Also, you make very good points about quality of life issues. I think that’s what makes the decision all the more difficult. Does one take transfusion dependency (and probably a very diminished QOL as a result) or use the EPO’s and be free to transfusions? To me it seems like an easy decision as long as one understands the risks of increasing their disease as a result. It really sucks having to choose between “which one will kill me first? Transfusions or EPO?”

Glad to hear you’ve had good QOL. Mom has too until just recently and we are very thankful for that.

patti

[Neil]

Hi Patti,
Take a look at the 2nd paragraph

“The drugs, sold by Amgen, Roche and Johnson & Johnson, are used to treat anemia caused by chemotherapy”
Towards the end of the article the writer mentioned:”It is not known why the drugs cause problems, if they do. It is known that raising hemoglobin levels too high increases the risk of blood clots. And most of these new trials did aim to increase hemoglobin above the levels recommended in the drugs’ labels, though that was not the case with Amgen’s own trial.”

Those of us with anemia as a result of MDS are taking Procrit/Aranesp because it has a very good chance of boosting Red cells. Not only do the manufacturers limit the dosage, they limit the administration of the drugs to an HGB level of 12.0 If one is over 12.0 they do not get an injection. Remember EPO and Darbepoietin are not FDA approved for the treatment of MDS. Those of us who take it find it boosts our energy levels to a point where we can live reasonably normal lives. My docs monitor my BP (usually 120/70) and check the blood vessels in my neck, legs and chest for any signs of blockage. With a platelet count of 10,000 one would not think clots would be an issue. Not necessarily true.

The QOL of those on TX varies. I know several MDS patients on TX that have a very good QOL. They go in after work on a schedule and have adapted to the routine quite well. One of them was on TX for about 15 years, made several trips to Russia on business. He was quite remarkable. Was even able to manage his iron overload caused by the TX.
If EPO is administered in recommended dosages there do not seem to have been many problems. At least that is the conclusion I came to after reading the reams of info on the potential side effects.
There are patients out there who self medicate the drug at home. This practice can lead to problems if one feels that the “more is better” approach is best for them.
Age is another factor. Have talked to a couple patients in their 40s with HGB in the mid 8s who are on Aranesp. Their counts are not increasing and it appears the Aranesp is not working. They both feel fine and have very few limitations. As they age the fatigue issues will become more complicated. Their choice —at the present time– is TX or an SCT. A rather serious and complicated decision. They view this time to be one of gathering all the info they can in order to make a decision when the time comes.
Am also inclined to think Dr Steensma (Mayo Clinic) has a very valid point.

A very dicey situation, with many issues and approaches.
Think about it

[patti]

[QUOTE]Originally posted by Carl:
[QB]

The drugs, sold by Amgen, Roche and Johnson & Johnson, are used to treat anemia caused by chemotherapy and meant to reduce the need for blood transfusions and give patients more energy.
[Q]

Neil,

You are correct. They are stating that these drugs are used to treat anemia caused by chemo. It was trials that were done that showed the risk of increasing cancers was done in people whose cancer’s themselves caused anemia (ie. MDS, leukemia).

Those are two different things. One is the drug company stating what the drugs are currently used for (ie, anemia caused by chemo – off label) and the second is the result of trials done on patients whose anemia is caused by cancer (not chemo). The information coming out now is the result of new drug trials (to change labeling info) on patients with cancers that CAUSE anemia.

That doesn’t change any of the what you said regarding QOL issues, etc. It’s just important, I think, to distinguish between those two statements in the article because they are two very different things.

Again, I think that if faced with choosing procrit/aranesp or transfusion dependency, most folks would choose the first over the latter. Not saying that’s a bad thing. I think it’s just instructive that it could in fact increase the disease itself – which is what we think occurred with my MIL. But we thought that long before this article ever came out.

I’m not saying one approach is better then the other. Just that this information coming out will certainly give folks more to have to consider when trying to decide the best course of treatment for themselves.

Patti

[Kiwi Ken]

This is great infomation
Many thanks
Ken

[Author]

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