My Friends for Life News

Tuesday, December 13, 2005

Status of Research supported by the Friends for Life Endowment at Dana Farber 12/2005

The Jimmy Fund 10 Brookline Place West
DANA-FARBER CANCER INSTITUTE Brookline, Massachusetts 02445-7226
(800) 52.JIMMY
617-632.4070 fax
www.jimmyfund,org


December 2, 2005



Dear Denyse & Michael:


As a leading academic cancer center, Dana-Farber has an obligation to both our patients and the medical community at large to produce the finest physician-researchers possible. Thanks to the Friends For Life Neuroblastoma Endowed Fellowship, the Institute continues to exceed this obligation, training the next generation of doctors at the forefront of cancer research and patient care.
Through her efforts to develop aggressive strategies and treatment programs for patients with neuroblastoma, Suzanne Shusterman, MD - the 2004-2005 Friends For Life Fellow -is bringing new hope to patients who relapse despite treatment they received for high-risk neuroblastoma. By supporting her work, the Friends For Life Neuroblastoma Endowed Fellowship is leading to more effective care and better outcomes for neuroblastorna patients around the world.

If you have any questions on this report or need additional assistance, please don't hesitate to contact me in the Development Office at (617) 632-3864. My best wishes for a happy and healthy new year.


Warmest regards,



Suzanne Fountain
Director, Jimmy Fund

CC: Suzanne Shusterman, MD


Dana-Farber Cancer Institute | Annual Report December 2005
Suzanne Shusterman, MD: Neuroblastoma

FRIENDS FOR LIFE NEUROBLASTOMA ENDOWED FELLOWSHIP

Research Overview

Neuroblastoma is a common pediatric tumor with a prognosis that is variable and dependent on both clinical features and tumor biology. While low risk neuroblastoma is often successfully treated with surgery alone, over one-half of patients are diagnosed with high-risk disease and require intensive multimodal therapy. Despite aggressive treatment, many children with high-risk disease relapse, and the prognosis for these children is poor. There is currently no curative treatment for patients who relapse necessitating a strong push for the development of novel strategies and treatment programs.


Research Highlights


DEVELOPMENT OF A THERAPEUTIC MIBG PROGRAM
Metaiodobenzylguanidine (MIBG) is a chemical that is selectively taken up by neuroblastoma cells. MIBG can be combined with radioactive iodine (131I) in the laboratory to form the radioactive compound 131I-MIBG. The 131I-MIBG compound delivers radiation specifically to the neuroblastotna cancer cells, causing them to die. 131I-MIBG has been used in more than 100 children in the United States to treat relapsed neuroblastoma and anti-cancer effects have been seen in about 40% of the cases. The majority of those treated have significant symptom relief, and MIBG has few side effects making it a very appealing treatment for relapsed patients. Currently, MIBG is only available at four pediatric centers in the United States: Children's Hospital of Philadelphia, University of California San Francisco, University of Michigan and Cincinnati Children's Hospital.

Over the past year, I have been developing a therapeutic MIBG program at Dana-Farber
Cancer Institute/Children's Hospital Boston. A working group, which meets monthly, has been established and consists of myself; Ted Treves, MD, Chief, Division of Nuclear
Medicine; Patricia Branowicki, RN, Vice President, Patient Medical Services; William
Lorenzen, Radiation Safety Officer; Royal Davis, CNMT, Technical Director, Nuclear
Medicine; Fred Fahey, DSc, Director, Nuclear Medicine Physics; Craig Hughey, Facilities Manager; Kathy Houlahan, Nurse Program Manager; and Jonathan Axon, Director,Strategic Planning. The group has designed plans for a lead lined room to be located on the current stem cell transplant floor and formulated a program budget and project request currently under review by CHB leadership. In addition, we have drafted a local protocol and initiated staff education. I anticipate that MIBG will be available in Boston within the next year.

DEVELOPMENT OF PROTOCOL FOR IMMUNE-BASED THERAPY FOR NEUROBLASTOMA
An alternative way to treat neuroblastoma is to trigger the body's immune system to fight off the disease. Hul4.18-IL2 is an experimental anticancer therapy designed to specifically bind to neuroblastoma cells and stimulate the immune system to attack and kill the tumor cells. Over the past two years, I have been collaborating with Dr. Paul Sondel at the University of Wisconsin to write a Phase II study for this antibody through the Children's Oncology Group. This study, of which I am co-chair opened last September and I am now working with investigators throughout the country to confirm eligibility and answer treatment questions. I am also seeking approval from the DFCI internal review board to make this study available soon for patients at the Institute. Results of this initial study will determine future development of the antibody.

DEVELOPMENT OF NANT PROGRAM AT DFCI
The NANT
(New Approaches to Neuroblastotna Therapy) consortium consists of 14 large children's hospitals dedicated to studying new therapies for relapsed neuroblastoma. Although DFCI was part of the NANT consortium before I started as the Friends For Life fellow, the program has grown significantly since my arrival. In August I hired a clinical research coordinator, Sharon Shang, who dedicates 50% of her time to NANT, which has increased both the number of open protocols and the therapeutic options available for relapsed patients. In my time at the Institute we have opened four new NANT studies (listed below, one more due to open in the next month) and have enrolled four patients.
NANT studies opened 10/04 - 11/05:
Phase I study of Oral Cyclophophamide and Zometa
Phase I study of Oral Irinotecan, Temozolamide and Cefixime
Phase I study of escalating doses of 131I-MIBG given in rapid sequence
Phase II study of MIBG followed by cyclophosphamide, etoposide and melphalan and
stem cell transplant
Phase I study of a novel formulation of fenretinide (soon to open)

DEVELOPMENT OF CLINICAL PROTOCOL FOR EVALUATION OF MINIMAL
RESIDUAL DISEASE

In collaboration with Dr. Judah Folkman, I am currently writing a protocol to collect blood and urine samples from neuroblastoma patients to measure angiogenesis-specific proteins at multiple time points during and after treatment. The goal is to identify a specific angiogenic profile that detects recurrent neuroblastoma before it becomes symptomatic and anatomically located by conventional methods. If successful, early treatment with angiogenesis inhibitors will be investigated to see if they improve the outcome of patients with relapsed disease.

The Impact of Your Support-Research Results and Next Steps
In collaboration with the Children's Oncology Group and Pfizer, Inc., I am in the early stages of writing a phase I study us' SU11248 - an inhibitor of growth receptors including the angiogenic agents PDGF and VEGF. This study will be open for all types of refractory solid tumors - including neuroblastoma - and might prove useful within the context of Dr. Folkman's research.

Recent Publications

Morowitz M, Barr R, Wang Q, King R, Rhodin N, Pawel B, Zhao H, Erickson SA, Sheppard GS, Wang J, Maris JM and Shusterman S. Functional validation of methionine aminopeptidase 2 as a molecular target for neuroblastoma therapy. Clinical Cancer Research 11:2680-5, 2005.

Shustertnan S and Maris JM. Prospect for therapeutic inhibition of neuroblastoma angiogenesis. Cancer Letters 28:171-9, 2005.

Maris JM and Shusterman S. Neuroblastoma. In Holland JC and Frei E (eds), Cancer Medicine, 7 th Edition BC Decker, Lewiston, NY, in press

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