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FDA News

FOR IMMEDIATE RELEASE
P06-64
May 3, 2006
   

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FDA Approves New Treatment for Myelodysplastic Syndromes (MDS)

The Food and Drug Administration (FDA) today approved Dacogen
(decitabine) injection for the treatment of myelodysplastic syndromes
(MDS). Dacogen is a new molecular entity that received orphan drug
status. Orphan products are developed to treat rare diseases or
conditions that affect fewer than 200,000 people in the U.S. The Orphan
Drug Act provides a seven-year period of exclusive marketing to the
first sponsor who obtains marketing approval for a designated orphan
drug.

Patients with MDS have bone marrow that does not produce enough mature
blood cells. This causes a lack of healthy blood cells that can
function properly in the body. Dacogen is thought to work by promoting
normal development of blood cells. Different types of MDS exist,
resulting in different manifestations of the disease. For example, some
patients with MDS require chronic blood transfusions.

“Today's approval of Dacogen offers patients with this rare disease an
additional treatment option that may help these patients avoid blood
transfusions,” said Steven Galson, MD, Director of FDA's Center for
Drug Evaluation and Research.

MDS can develop following treatment with drugs or radiation therapy for
other diseases or it can develop without any known cause. Some forms of
MDS can progress to acute myeloid leukemia (AML), a type of cancer in
which too many white blood cells are made.

An estimated 7,000 to 12,000 new cases of MDS are diagnosed yearly in
the United States. Although MDS occurs in all age groups, the highest
prevalence is in people over 60 years of age. Typical symptoms include
weakness, fatigue, infections, easy bruising, bleeding, and fever.

The safety and effectiveness of Dacogen were demonstrated in a
randomized, controlled trial where patients received either Dacogen or
the standard therapy and in two non-randomized studies where all of the
patients received Dacogen. The new drug was evaluated in a total of 268
patients. About 22% of patients in the three trials had complete or
partial responses to Dacogen. Responses consisted of complete or
partial normalization of blood counts and of fewer immature cells in
the bone marrow. In responders the need for transfusions was eliminated
during the period of response.

The most common side effects reported in clinical trials included
neutropenia (low white blood cell count), thrombocytopenia (low
platelets in blood), anemia, fatigue, fever, nausea, cough, bleeding in
the skin, constipation, diarrhea, and hyperglycemia (high blood sugar).

Dacogen is manufactured by Pharmachemie B.V. Haarlem, The Netherlands
for MGI PHARMA, INC., Bloomington, MN.

####

http://www.jco.org/cgi/content/abstract/24/3/476

 Journal of Clinical Oncology, Vol 24, No 3 (January 20), 2006: pp.
476-483
© 2006 American Society of Clinical Oncology
DOI: 10.1200/JCO.2005.02.7235

Risk of Selected Subsequent Carcinomas in Survivors of
Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Mylène Bassal, Ann C. Mertens, Leslie Taylor, Joseph P. Neglia, Brian
S. Greffe, Sue Hammond, Cécile M. Ronckers, Debra L. Friedman, Marilyn
Stovall, Yutaka Y. Yasui, Leslie L. Robison, Anna T. Meadows, Nina S.
Kadan-Lottick

From the Division of Pediatric Hematology/Oncology/BMT, University of
Colorado Health Sciences Center, Denver, CO; Department of Pediatrics,
University of Minnesota School of Medicine, Minneapolis, MN; Cancer
Prevention Research Program, Fred Hutchinson Cancer Research Center,
Seattle, WA; Department of Pathology, Ohio State University, Columbus,
OH; National Cancer Institute, Division of Cancer Epidemiology and
Genetics, National Institutes of Health, Department of Health and Human
Services, Bethesda, MD; Department of Pediatrics, University of
Washington, Fred Hutchinson Cancer Research Center, Seattle, WA; The
University of Texas M.D. Anderson Cancer Center, Houston, TX;
Department of Public Health Sciences, University of Alberta Edmonton,
Canada; Department of Pediatrics, University of Pennsylvania School of
Medicine, Philadelphia, PA; Department of Pediatrics, Section of
Pediatric Hematology-Oncology, Yale University School of Medicine, New
Haven, CT

Address reprint requests to Nina S. Kadan-Lottick, MD, MSPH, Yale
University School of Medicine, 333 Cedar St, LMP 2073, PO Box 208064,
New Haven, CT 06520; e-mail: nina.kadan-lottick@yale.edu

PURPOSE: To determine the risk of subsequent carcinomas other than
breast, thyroid, and skin, and to identify factors that influence the
risk among survivors of childhood cancer.

PATIENTS AND METHODS: Subsequent malignant neoplasm history was
determined in 13,136 participants (surviving ≥ 5 years postmalignancy,
diagnosed from 1970 to 1986 at age < 21 years) of the Childhood
Cancer Survivor Study to calculate standardized incidence ratios
(SIRs), using Surveillance, Epidemiology, and End Results data.

RESULTS: In 71 individuals, 71 carcinomas were diagnosed at a median
age of 27 years and a median elapsed time of 15 years in the
genitourinary system (35%), head and neck area (32%), gastrointestinal
tract (23%), and other sites (10%). Fifty-nine patients (83%) had
received radiotherapy, and 42 (59%) developed a second malignant
neoplasm in a previous radiotherapy field. Risk was significantly
elevated following all childhood diagnoses except CNS neoplasms, and
was highest following neuroblastoma (SIR = 24.2) and soft tissue
sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold
increased risk of renal cell carcinomas; survivors of Hodgkin's
lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas.
Significantly elevated risk of head and neck carcinoma occurred in
survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR =
20.9), and leukemia (SIR = 20.9).

CONCLUSION: Young survivors of childhood cancers are at increased risk
of developing subsequent carcinomas typical of later adulthood,
underscoring the importance of long-term follow-up and risk-based
screening. Follow-up of the cohort is ongoing to determine lifetime
risk and delineate individual characteristics that contribute to risk.

Supported by Grant No. U24-CA55727 from the National Institutes of
Health and by funding provided to the University of Minnesota by the
Children's Cancer Research Fund. N.S.K.-L. was supported in part by
Grant No. K12RR17594 from the National Center for Research Resources.

Presented in part at the 40th Annual Meeting of the American Society of
Clinical Oncology, New Orleans, LA, June 5-8, 2004 (poster discussion).

Authors' disclosures of potential conflicts of interest and author
contributions are found at the end of this article.

http://www.nci.nih.gov/clinical_trials/view_clinicaltrials.aspx?cdrid=68407&version=healthprofessional

Study of Late Effects Due to Treatment in Patients Previously Treated for
Pediatric Sarcoma
Last Modified: 12/10/2002     First Published: 2/1/2001  

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Projected Accrual
Outline
Published Results
Trial Contact Information

Alternate Title

Long-Term Effects of Therapy in Patients Previously Treated for Childhood
Soft Tissue Sarcoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Supportive care Active 2 and over NCI NCI-01-C-0037C

Special Category: NIH
Clinical Center trial

Objectives

1. Determine the incidence and degree of functional
   musculoskeletal impairment, late cardiac dysfunction induced by doxorubicin,
   gonadal dysfunction induced by alkylator-based chemotherapy and/or radiotherapy,
   and metabolic stress syndrome induced by dose-intensive chemotherapy in patients
   previously treated for pediatric sarcoma.
2. Determine whether these patients have diminished
   bone mineral density.
3. Correlate gonadal dysfunction and metabolic stress
   syndrome with loss of bone mass in these patients.
4. Determine the quality of life of these patients.
5. Determine the frequency and patterns of adaptational
   and adjustment difficulties with distinction of clinical or subclinical psychiatric
   illness in these patients.
6. Determine myocardial tissue changes associated
   with anthracycline therapy and the cardiac function of patients treated with
   or without the cardioprotectant dexrazoxane.
7. Determine the incidence and frequency of secondary
   malignancies, hepatitis B, C, or HIV seroconversion, and ifosfamide-related
   renal dysfunction in these patients.
8. Determine the T-cell depletion following chemotherapy
   in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of sarcoma in first remission or continued
  remission of more than 5 years after completion of salvage therapy for disease
  relapse
  • Stable disease for more than 24 months

    OR

  • No evidence of disease
• Prior enrollment on a National Cancer Institute
  Pediatric Oncology Branch (POB) protocol or the Natural History protocol
  and treated according to POB outlines for sarcomas
• Received prior chemotherapy according to prior
  POB trial

Prior/Concurrent
Therapy:

Biologic therapy:

• At least 24 months since prior immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 24 months since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 24 months since prior radiotherapy

Surgery:

• At least 24 months since prior surgery for cancer

Patient Characteristics:

Age:

• 2 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test

Projected Accrual

Approximately 50-100 patients will be accrued for this study
within 1-2 years.

Outline

Patients undergo evaluation of the following: cardiac dysfunction
by echocardiogram, MUGA scan, and cardiac MRI with gadolinium texaphyrin
contrast; gonadal dysfunction by physical examination, endocrine testing,
and semen analysis; hormonal stress by serum hormone levels; musculoskeletal
impairment by bone densitometry and musculoskeletal and functional testing
by rehabilitation medicine specialists; transfusion-associated risks by
hepatitis A, B, C, HIV, and HTLV-1 testing; and other major organ impairments.

Quality of life and psychosocial effects (including post-traumatic
stress syndrome) are also assessed.

Disclaimer

The purpose of most clinical trials listed
in this database is to test new cancer treatments, or new methods of diagnosing,
screening, or preventing cancer. Because all potentially harmful side effects
are not known before a trial is conducted, dose and schedule modifications
may be required for participants if they develop side effects from the treatment
or test. The therapy or test described in this clinical trial is intended
for use by clinical oncologists in carefully structured settings, and may
not prove to be more effective than standard treatment. A responsible investigator
associated with this clinical trial should be consulted before using this
protocol.

Published Results

Mansky PJ, Hoffman K, Derdak J, et al.: Preserved functionality and increased
cardiovascular disease risk in pediatric sarcoma long-term survivors. [Abstract]
Proceedings of the American Society of Clinical Oncology 22: A-3261, 2003.

Mansky PJ, Lawande N, Long L, et al.: MRI evidence for cardiac remodeling
in longterm pediatric sarcoma survivors of doxorubicin therapy. [Abstract]
Proceedings of the American Society of Clinical Oncology 21: A-1559, 2002.

Wiener L, Battles H, Long L, et al.: Persistent psychological distress
in long-term survivors of pediatric sarcoma. [Abstract] Proceedings of the
American Society of Clinical Oncology 21: A-2912, 2002.

Trial Contact Information

Trial Lead Organizations

NCI – Center for Cancer Research

Patrick Mansky, MD, Protocol chair		Ph: 301-435-4845 Email: manskyp@mail.nih.gov 1

Trial Sites and Contacts

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center – NCI Clinical Studies Support
		Patient Recruitment	Ph:  888-NCI-1937

Table of Links

http://www.ingenta.com/isis/searching/Expand/ingenta?pub=infobike://hum/crbmm/2004/00000002/00000002/art00003

Effects of Drug Treatment for Malignancy on Skeletal Health of Cancer Survivors
 

Clinical Review in Bone and Mineral Metabolism  

June 2004, vol. 2, no. 2,  
pp. 103-114(12)
 
Heras-Herzig A.; Guise T.A.
 
Abstract:
Cancer treatment has advanced and survivorship is increasing. As
such, a new skeletal complication of malignancy, cancer treatment-induced
bone loss, has emerged and is likely to be the most common skeletal complication
of malignancy in years to come. Therapy for the most common cancers, breast
and prostate, often results in sex-steroid deficiency and subsequent bone
loss. A significant portion of breast cancers express estrogen receptors,
and estrogen stimulates tumor growth. Therapy directed against estrogen action
or to reduce estrogen production results in significant survival advantage
in women with estrogen receptor-positive breast cancer. This hormonal therapy
represents the mainstay of breast cancer treatment and is highly effective.
Many breast cancers are also treated with chemotherapy, which often induces
transient or permanent ovarian failure. However, estrogen is a critical factor
for maintaining bone health and normal bone mineral density. As such, all
of these breast cancer therapies may induce bone loss, mainly by reducing
estrogen or its action on bone. Aromatase inhibitors fall into this category;
its efficacy dictates that it will become first-line therapy for most hormone-sensitive
breast cancers. Theoretically, chemotherapy may have direct effects on bone
that are independent of the effects of estrogen deficiency, but evidence
is lacking. Limited clinical experience indicate that bisphosphonates are
effective in preventing bone loss owing to cancer treatment. This article
focuses on therapy for breast cancer and other malignancies and the respective
contributions of such therapy to bone loss.
 
Keywords: Bone; malignancy; antineoplastic
drugs; bone loss; skeletal health; osteoporosis
 
Document Type:
Miscellaneous ISSN: 1534-8644

Publisher:

Humana Press