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Re: Zevalin, Dr. Furman's comments

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Dr. Furman:

What do you think of the recently trial announced at the Hutchinson

center in Seattle, where they treat patients with RF (6 cycles), and

after confirmatory bone marrow biopsy to make sure bone marrow

involvement is below 20%, using Bexxar (sister compound to Zevalin)

for MRD clean-up? Even very late stage patients with follicular

lymphoma have gotten fantastic remissions with just one single

infusion of Bexxar (not counting the small dosimetric dose). And the

toxicity was way below anyting we see in combinations such as RF (or

R + HDMP) followed by Campath for MRD clean up.

Is it reasonable to test Bexxar and / or Zevalin in CLL patients,

provided they first go through cytoreduction to decrese bone marrow

involvement?

CLL Topics did a big review on this subject and the Hutch trial.

Larry

>

> Terry,

> Your wife has certainly been through a great deal. It is always

important

> to above all else, do no harm. But of course, trying to push

forward and

> improve the situation is what keeps all of us going. At first

glance, I

> would not be very interested in Zevalin. I, in general, have a

bias away

> from Zevalin for CLL patients. Zevalin is an antibody against

CD20, like

> rituximab, that is bound to a radioactive Ytrium molecule. The

antibody

> serves the purpose of carrying the radiation directly to the CLL

cells,

> hopefully avoiding the normal tissues. The problem with using

Zevalin in

> CLL patients is that since so much of their disease is in the

marrow, the

> radioactivity concentrates in the marrow and causes severe

cytopenias.

>

> It is unclear whether your wife's situation is the result of the

> hypercalcemia only or are there cytopenias as well? One option

that might

> help is Campath. Campath works very nicely on the marrow

involvement and

> can help improve blood counts to enable patients to become

stronger. Many

> people (patients and physicians) are very hesitant to use Campath

because

> of the immunosuppression. I find that if properly observed, the

> immunosuppression is very manageable. I follow CMV peripheral

blood PCR

> every 1-2 weeks and make sure patients are receiving Valtrex and

Bactrim

> prophylaxis. Other supportive therapies are also important, like

IV Ig to

> replace antibodies missing because of the hypogammaglobulinemia.

The IV Ig

> might be a good idea for her regardless of what additional

therapies she

> does, especially in light of her recent blood infection.

>

> Another option is to use rituximab in the hopes of enabling her to

have

> enough time to become stronger and tolerate more aggressive

therapy. I

> hope this helps.

>

> Rick Furman, MD

>

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This article appeared in the Science Daily from a UPI wire:

TWO LYMPHOMA DRUGS UNDERUSED

NEW YORK, July 14 (UPI) -- Two drugs proven successful against

lymphoma rarely are prescribed because market-driven forces distort

medical decisions, it was reported Saturday.

Bexxar and Zevalin are federally approved for lymphoma, but fewer

than 10 percent of suitable candidates for the drugs received them

last year, The New York Times reported.

" It is astounding and disappointing " Bexxar and Zevalin are used so

little, said Dr. Oliver W. Press, chairman of the scientific advisory

board of the Lymphoma Research Foundation.

Oncologists often repeatedly prescribe other drugs, even after they

have lost their effectiveness, when Bexxar and Zevalin might work

better, Press said.

Oncologists often have financial incentives to use drugs other than

Bexxar and Zevalin, which they are not paid to administer, Press

said. In addition, using either drug usually requires doctors to

coordinate treatment with academic hospitals, which the doctors may

view as competition, the Times reported.

Copyright 2007 by United Press International. .

http://www.sciencedaily.com/upi/index.php?feed=Science & article=UPI-1-

20070714-13201400-bc-us-cancerdrug.xml

If true, pretty astounding, if not shocking.

Any comments?

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Everyone,

I was hoping to not have to comment on the NY Times article, but now I

will. This article presents a very one-sided perspective to the use of

Bexxar and Zevalin, and very little of it is relevant to CLL patients. The

articles discusses case stories of several patients who did wonderfully

well with these agents. But it must remember that they are the minority

(vast minority) of cases. Most patients had minimal benefit, and even some

had completely disastrous outcomes, with long-term, persistent

pancytopenia. These drugs are probably best used in only a rare situation.

While the facts surrounding the " reimbursement " issues are correct, I do

not believe that it is the main reason for the drugs not being used. At

this point I will have my disclaimer. What the article discusses is that

when medical oncologist administer chemotherapy in their office, they are

able to bill and make a significant amount of money from these

billings. This would potentially be a motivation for not referring a

patient to a nuclear medicine physician to administer Bexxar or Zevalin, as

the nuclear medicine physician would get the billings from the

administration of these agents. This only holds true for physicians in

private practice. Those of us in academic practices do not generate any

revenue from administering chemotherapy, and thus would not have any

motivation to keep the patients from receiving these agents. I can thus

speak without any appearance of financial bias.

What concerns most physicians about these agents is that once they are

administered you are stuck. If they work, then it is great. If they do

not work, then patients are often left with no options because the

radiation exposure they have received oftern prevents them from being able

to receive any other treatments. Overall, it is this sense of a " point of

no return " that mostly limits medical oncologists.

Rick Furman, MD

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