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August 18, 2003 Myeloma Minute
What's News
Question of the Week:

Q. Is Zometa safe for myeloma patients? Should I switch to Aredia? There has been an article circulating on the myeloma list serve about a number of myeloma patients who had kidney failure as a result of taking Zometa.

A. Aredia (pamidronate) and Zometa (zoledronate or zoledronic acid) are the two drugs currently approved by the Food and Drug Administration for use in preventing bone disease in multiple myeloma. They belong to a class of drugs called "bisphosphonates." Aredia was approved in 1996 and became the standard of care for myeloma patients. It has become established as a very safe, helpful drug for the treatment of myeloma bone disease. Zometa was approved in early 2002 based upon study results comparing it with Aredia. Zometa produces more rapid and prolonged reduction in elevated blood calcium when elevated levels are present. However, results evaluating the effects on skeletal related events ("SREs"--tumors and holes in the bone) showed that Zometa and Aredia affect SRE's equivalently. The major difference with Zometa, therefore, proved to be its much shorter infusion time of 15 minutes versus 2 to 4 hours for Aredia.

The most common side effects of either drug are fever, vein irritation at the site of the infusion, general aches and pains, and kidney dysfunction. Fever associated with bisphosphonates is typically mild (i.e. 100 degrees to 101 degrees), occurring a few hours after intravenous infusion and lasting for a few hours at most. Fever is usually easily treated or prevented with 1 or 2 Tylenol (325 mg per tablet).

The main additional concern relates to kidney side effects. All bisphosphonates are potential toxins for the kidneys. Since myeloma can have an impact on kidney function (due to myeloma protein damage or elevated blood calcium), the possibility of kidney-related side effects is of particular concern. Aredia has been used widely for almost 10 years, including the initial trials period. The main toxicity that has emerged is a type of protein loss in the urine (albuminuria or nephrotic syndrome). This toxicity has occurred predominantly with uses of higher than recommended doses (e.g. 180 mg versus 90 mg) and/or more frequent than recommended dosing schedules (e.g. every two weeks instead of once a month). This side effect is usually reversible with dose and/or schedule adjustments or, in occasional severe cases, discontinuing Aredia. Very rare irreversible damage has occurred. Periodic monitoring (e.g. every 3 to 6 months) of urine protein levels with 24-hour urine collection is recommended to prevent any significant kidney damage from Aredia.

Zometa, on the other hand, has only been in clinical use for 18 months. The major toxicity-related concern that has emerged with Zometa is an increase in serum creatinine, which is an indication of kidney dysfunction. Reports of both increased creatinine and occasionally more severe kidney damage, acute tubular necrosis, within the first year have raised concerns that this much more potent bisphosphonate must be used more cautiously with respect to kidney function.

The article which is being referred to on the list serve was published in Kidney Int. 2003 Jul; 64(1): 281-289, entitled "Toxic acute tubular necrosis following treatment with zoledronate (Zometa)." The authors, from the departments of pathology, nephrology, and internal medicine at Columbia Presbyterian Hospital in New York, Morristown Memorial Hospital in New Jersey, and Community Medical Center in East Toms River, New Jersey, evaluated six patients who had kidney failure after receiving Zometa (five of them diagnosed with myeloma, the sixth with Paget's Disease of the bone). All six of the patients had bone disease, and all received pamidronate (Aredia) before being switched to Zometa. Of note: none of the six patients had previous evidence of kidney disease. The mean duration of Zometa therapy for these patients was 4.7 months before renal failure occurred. All had received the correct, recommended dose: 4 mg of Zometa once a month, infused over at least 15 minutes.

In addition, three abstracts presented at the most recent ASCO (American Society of Clinical Oncology) meetings in Chicago, raised concerns about kidney toxicity with Zometa and, as in the above article, particularly in patients switching from Aredia to Zometa.

As a result of similar reports from around the country, Novartis, the company that makes both Aredia and Zometa, has proposed a set of guidelines for physicians who treat myeloma patients. These guidelines include the following precautions:

  • Be especially cautious with the use of Zometa if there is concern from the outset for kidney dysfunction—i.e. with Bence Jones myeloma, diabetes, long-standing high blood pressure, or in elderly or frail patients. Do not use Zometa in patients with known kidney deterioration, especially if the creatinine value is over 3 mg/dl.

  • Check the serum creatinine level before each dose of Zometa.

  • If the serum creatinine value has increased by > (greater than or equal to) 0.5 mg/dl in a patient with normal renal function at the outset, the doctor should hold the next dose until the value returns to within 10% of baseline.

  • For those patients who have experienced mild elevations in serum creatinine values that have returned to 10% of baseline, adjustments to the treatment schedule may be considered, to include increasing the time of infusion from 15 minutes to 30 or 45 minutes, using larger volumes of diluting fluids, or delaying the administration of the next dose. The treating physician should use his/her clinical judgment to determine which option is the most appropriate for an individual patient.

  • Certain drugs that may affect kidney function could be more likely to do so if they are given concurrently with bisphosphonates. Some examples of these medications may include nonsteroidal anti-inflammatories (NSAIDs), thalidomide, and certain antibiotics.

In order to avoid an infusion rate that is more rapid than planned or anticipated, an infusion time of 30 minutes can be strongly considered. Using a 30 minute infusion time provides some leeway for the infusion center and can help prevent Zometa from ever being infused in less than 15 minutes.

With the above caveats in mind, you should be scrupulous in discussing with your doctor whether or not Zometa is an appropriate choice for you, and in turn, your doctor should be scrupulous in monitoring your serum creatinine level before your monthly infusion of bisphosphonates.

What's New in Research:

Newly Identified Tumor Suppressor Cooperates With p53 to Protect Mice Against Tumors
In a study published in the Aug. 8, 2003, issue of the journal Cell, researchers at the National Cancer Institute demonstrate that reducing or eliminating the H2AX gene in mice that lack p53, a well-known tumor suppressor gene, causes an increase in the number of tumors that develop.

What's New in Clinical Trials:
  • Phase I Trial of VELCADE and Thalidomide. Phase I exploratory study of combination VELCADE and Thalidomide in refractory multiple myeloma. Investigator: Bart Barlogie, MD, PhD 501-526-CARE (2873)

  • Phase I/II Trial of VELCADE + Adriamycin + Dexamethasone. (UK only) Phase I/II study to assess the safety, efficacy, and tolerability of combination therapy with VELCADE, Adriamycin, and dexamethasone (PAD) as primary therapy for patients with multiple myeloma. Investigator: Jamie Cavanaugh, MD +440 207 601 8202
  • Myeloma Matrix (updated 08/07/03)
    The Myeloma Matrix provides updated information about drugs beginning with pre-clinical developments and tracks drugs as they proceed through Phases I – III of clinical trials, drugs that have been FDA approved, and information on trials that are being conducted by NCI- sponsored cooperative groups as well as other myeloma study groups. The online version is updated regularly. If you would like to have a printed copy, call the toll-free hotline (800) 452-2873.

  • Cancer Trials Support Unit: A Web Based System That Offers Efficient and Effective Tools for Clinical Trials Management.
    The Cancer Trials Support Unit (CTSU) is an NCI funded program to facilitate participation (by both patients and physicians) in phase III NCI sponsored Cancer treatment trials.

If you would like to browse trials currently open for enrollment, visit the Clinical Trials page of the IMF web site. Among the links, you will find CenterWatch and EmergingMed. The IMF has entered into partnerships with them to assist you in matching trials to your particular patient profile (i.e., stage of disease, previous treatment, how well you are able to carry out the activities of daily living, etc.) and by doing so, increase your chances of being eligible. You can also learn more about clinical trials by reviewing materials from the National Cancer Institute.

Advocacy Update:
Upcoming Seminars and Conferences:
Upcoming Fundraisers:

FUNdraising Made Easy
You know you want to do something, but deciding on what to do can be confusing. The IMF can help. This year, our members really rallied 'round the cause, picked up the gauntlet, and raised a lot of money for myeloma research and programs. We are already getting calls from new members who want to join in the effort and hold an event in 2004. Suzanne Battaglia is waiting for your call. She is here to help you plan and execute your event, so please write, call or email (SBattaglia@myeloma.org) so that you can get on our Calendar of Events! See what you can do in your community to help further the goal of finding the cure!

Ralph Ferrizzi Memorial Golf Tournament
August 23, 2003
Allentown, PA

Exciting Opportunities
  • Ribbon of Hope Making A World of Difference Anniversary Gala
    October 4, 2003
    Paul Allen's Experience Music Project Museum in Seattle, WA

    The evening promises to be the best ever, both creatively and financially! The EMP is Seattle's most unique architectural wonder. The Frank O. Gehry-designed building houses a new interactive museum that combines performance space, technology and revolutionary architecture in a facility created to celebrate the heritage and anticipate the future of American popular music.

  • Third Multiple Myeloma Quilt of Courage is Online
    The third quilt is finished and on the web. Like the two before it, it is both beautiful and moving. Take a look for yourself.

    Several people who purchased squares for the 4th and final quilt were not able to complete them. Therefore, we have had to send out new squares to people on a waiting list, and we are now waiting for them to return their finished squares. They've been given a deadline of mid to end of August, so we're hoping to have the 4th quilt up on our web site by the first week in September. For all of you who finished and sent back your 4th quilt square in a timely fashion, we apologize for the delay.

  • GTC Telecom is reaching out on behalf of the IMF with a wonderful new way for you to help fight myeloma while saving yourself money at the same time!
    By signing up for the new IMF Long Distance Plan, 10% of what you spend on your long distance calls every month will be directly donated to the International Myeloma Foundation. This fantastic long distance plan offers you savings of up to 40% or more over what you may currently be paying! Click on the link to find out more.

Items of Interest:
    BANK ON A CURE® is an innovative and powerful concept designed to establish a method to find new treatments for multiple myeloma and other related diseases as well as the possibility of new cures, while customizing care for current patients.
  • International Prognostic Index
    The International Myeloma Foundation is proud to sponsor the International Prognostic Index (IPI) Classification for Multiple Myeloma. Nearly twenty myeloma institutions from around the world are collaborating to create an updated staging system for multiple myeloma.
  • NexCura Cancer Profiler
    The Cancer Profiler is a free service (no hidden fees or charges). Its tools provide you with information specific to your cancer diagnosis to help you make more informed treatment decisions along with your physician.
  • Expert Opinions on Multiple Myeloma
    A multimedia, CME-accredited program for physicians with the chance to see world-renowned myeloma specialists sharing their knowledge, discussing treatment choices, and comparing their perspectives on controversial issues in multiple myeloma and related diseases.
  • MMInteractive
    An exciting new way for myeloma patients to get involved at patient seminars.
  • Myeloma At The Movies
    It has been our goal to bring our Patient & Family Seminars to people around the country who might not be able to attend an actual meeting, so we have set up a video lending library. New tapes have recently been added from the Seattle Patient & Family Seminar.
  • The Catlett Card Series
    The Catlett Cards are designed by Irma Catlett in memory of her husband Lou. The stunning pictures on these cards chronicle their travels together and honor Lou and the life they shared. Blank on the inside, they are perfect for thank-you's, birthdays, anniversaries, and just general correspondence. All proceeds go to support the programs of the IMF.
  • IMFers Esther and Herman Adler, of Adler & Company Jewelers in Los Angeles are continuing their generous offer to help the IMF. Buy beautiful jewelry at wholesale prices and—if you tell them you are an IMFer—a portion of the proceeds will be donated to the IMF. They make it so easy, too. They can work from digital pictures if you cannot meet with them, and they have a return policy if you are not completely satisfied. Call them at 213-624-1945 for more information.

Shop for the Cure!

Many of the internet's most popular merchants will donate a portion of your purchases to the IMF if you enter their sites using the links on our Shop For The Cure page. You can also use the special shortcut URLs listed below:

So, Shop For The Cure by using these links to the same get great service and low prices you're used to while helping support the IMF!

Help Us Help Others...
As a non-profit organization, the IMF is completely dependent on the support of our members. Please consider showing your support by making a tax-deductible donation today. Donations in honor of a friend or family member make great gifts and are a wonderful way to celebrate a special occasion. You can donate online or by calling the IMF at (800) 452-CURE. We sincerely thank you for your support.

Tell A Friend...
The Myeloma Minute is a great way to stay abreast of the latest developments within the myeloma community. We hope you'll share this information with friends, family members and physicians and encourage them to sign up for their own copy by forwarding this message. New users can register by clicking here.

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