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| NATIONAL INSTITUTE |
| C A N C E R |
| INTERNATIONAL INFORMATION |
| C E N T E R |
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CancerNet has been updated for April. The following statements
were modified.
Changes to the Cancer Information Statements
{*filter*} acute lymphocytic leukemia cn-101024
{*filter*} Hodgkin's disease cn-100003
{*filter*} non-Hodgkin's lymphoma cn-100066
{*filter*} soft tissue sarcoma cn-100921
{*filter*}cancer cn-100022
Bladder cancer cn-101206
{*filter*} cancer cn-100013
Chronic lymphocytic leukemia cn-101003
Chronic myelogenous leukemia cn-101031
Cervical cancer cn-100103
Colon cancer cn-100008
Cutaneous T-cell lymphoma cn-100098
Endometrial cancer cn-100089
Ewing's sarcoma cn-100021
Gastric cancer cn-100025
Intraocular melanoma cn-101279
Islet cell carcinoma cn-100790
Lip and {*filter*}cavity cancer cn-102840
Malignant thymoma cn-101248
Melanoma cn-101302
Neuroblastoma cn-100530
Nonsmall cell lung cancer cn-100039
Osteosarcoma cn-100049
Ovarian epithelial cancer cn-100950
Pancreatic cancer cn-100046
Health InfoCom Network News Page 3
Volume 6, Number 8 April 4, 1993
Parathyroid cancer cn-100541
Pituitary tumor cn-101273
Plasma cell neoplasm cn-100281
Prostate cancer cn-101229
Renal cell cancer cn-101070
Small cell lung cancer cn-100040
Testicular cancer cn-101121
Vulvar cancer cn-101038
Wilms' tumor cn-100719
Patient statements:
{*filter*} non-Hodgkin's lymphoma cn-200066
Childhood non-Hodgkin's lymphoma cn-200915
Malignant thymoma cn-201248
Neuroblastoma cn-200530
Parathyroid cancer cn-200541
Testicular cancer cn-201121
Vulvar cancer cn-201038
Changes to Supportive Care and Screening Guidelines
Constipation, impaction, and bowel obstruction cn-303510
Hypercalcemia cn-304462
Lymphedema cn-300442
{*filter*}complications secondary to cancer therapy cn-302904
Skin integrity changes secondary to cutaneous metastases cn-304277
Superior vena cava syndrome cn-304708
Screening for {*filter*} cancer cn-304723
Screening for skin cancer cn-304724
Request the Monthly PDQ Statement Changes (cn-305001) for a description
of the changes in the statements listed above.
News items:
Health InfoCom Network News Page 4
Volume 6, Number 8 April 4, 1993
PDQ Distributors cn-400003
Cancerlit Distributors cn-400006
PDQ Voluntary Protocol Submission General Information cn-400010
Group C protocol information cn-400014
NCI High Priority Clinical Trials cn-400007
NCI-designated Cancer Centers cn-400008
Instructions:
To request the CancerNet Instructions and Contents List, send a mail message,
leaving the subject line of the message blank, and in the body of the message,
enter HELP. Address the mail message to:
To request the modified statements, follow the above directions, and in the
body of the mail message, enter the statement code. When requesting more than
one statement, enter each code on a separate line.
CancerNet statements are now available in Spanish. To request the Instructions
and Contents List in Spanish, enter SPANISH in the body of the mail message.
If you would like to request the statements in Spanish, substitute the prefix
"cs-" in front of the number (e.g., cs-100022 to receive the statement on {*filter*}
cancer in Spanish). All of the physician and patient statements are available
in Spanish. Supportive care statements and Cancer screening guidelines are not
currently available in Spanish. News items that are available in Spanish have
a # next to the statement title. Although both the English and Spanish are
updated at the same time each month, the Spanish statements do not reflect the
changes made in the English statements until the following month( to allow
time for translation). If you are interested in requesting CancerNet
statements or news articles in Spanish, it is suggested that you request an
updated Contents List.
If you are redistributing the PDQ information you retrieve from CancerNet to
others at your location, the ICIC would be interested in hearing how you reuse
the information, how useful you find it, etc. Additionally, we may be able to
suggest ways to enhance your use of the information or we may have other
information that would be useful to you. Please send responses to:
Cheryl Burg
NCI International Cancer Information Center
Health InfoCom Network News Page 5
Volume 6, Number 8 April 4, 1993
Huntington Disease Gene is Found
Huntington's Disease Society of America
Press Release March 23, 1993
Research Breakthrough:
Huntington's Disease Gene is Found
An international team of scientists, led by Dr. James Gusella of
Massachusetts General Hospital, Boston, Massachusetts, has identified the
gene which causes Huntington's Disease, a hereditary neurological
disorder which is always fatal and for which there is no treatment or
cure.
After nearly 10 years of intensive, collaborative effort, the
scientists have discovered a variation in the coding for a gene on
chromosome 4 occurring in people affected by Huntington's Disease
(HD). The scientists have done exhaustive research with hundreds of
{*filter*} samples to establish that this variation is actually responsible
for the illness. How this variation in the genetic coding causes HD has
not been established and will require a great deal more research.
Although it is expected that the procedure for predictive testing
for HD will be simplitied, there is still no cure or treatment for the
disease. Studies will now focus on the tissues, organs, or cell types in
which the gene is normally expressed, the gene's normal role, and how its
expression is altered in HD.
The collaborative research team includes Francis Collins of the
University of Michigan; John Wa{*filter*}h of the University of California at
Irvine; Hans Lehrach and Anne-Marie Frischauf at the Imperial Cancer
Research Center in London, England; David Housman, Massachusetts
Institute of Technology; Peter Harper, University of Cardiff, Wales; and
James Gusella.
Major financial support for this research has been provided by the
National institute of Neurological Disorders and Stroke, the Huntington's
Disease Society of America, and the Hereditary Disease Foundation.
The Huntington's Disease Society of America (HDSA) is a national
organization with 31 chapters throughout the United States, dedicated to
ensuring care and support for people affected by HD and their families,
and to finding a cure through research.
At leagt 25,000 Americans are known to be affected by HD, and an
additional 125,000 are at risk of inheriting it from an affected parent.
First symptoms of HD are usually detected in mid-life, and the disease
runs a devastating, degenerative course.
For further information on HD, HDSA, or the recent research
developments, call HDSA's national office at (800) 345-RDSA or (212) 242-
1968.
Health InfoCom Network News Page 6
Volume 6, Number 8 April 4, 1993
Huntington Disease Gene Found
By Dr. Richard H. Myers
After nearly ten years of effort, an international team of scientists
headed by Dr. James P. Gusella in Boston has successfully identified the
gene which causes Huntington's Disease.
What Was Found?
A variation in the genetic code for a gone on chromosome 4 was found
among persons affected with Huntington's disease. Normally, the genetic
code of this gene has three DNA bases, CAG, which are repeated several
times. Among persons with Huntington's disease, the number of repeats of
this sequence approximately doubles.
Hundreds of Huntington's disease and normal {*filter*} samples were studied to
establish that this variation is specific to Huntington's disease gene
carriers and actually is responsible for the illness. How this variation
in sequence causes Huntington's disease has not been established. Much
more research will be needed to determine the exact mechanisms which
cause brain cells to die in Huntington's disease.
What Does This Mean for Me?
In the immediate future, there will be no changes. The methods for the
treatment or diagnosis of Huntington's disease will remain the same for
some time.
However, with further investigation, new possibilities will arise for
persons at risk for Huntington's disease. Until now, many {*filter*}
specimens were necessary for a genetic test. Once the procedure has been
validated, it is expected that a test will be possible with only a {*filter*}
sample from the person wishing to be tested. In addition, testing will
become less complex and less expensive.
Nevertheless, genetic testing in Huntington's disease remains a personal
decision which should be considered very carefully. Although the test is
expected to become technically less complex, the personal implications
will remain substantial and it is necessary that testing continue to be
carried out through a program of appropriate counseling.
Is there a Cure for Huntington's Disease?
There is neither a cure nor a treatment for Huntington's disease. The
Health InfoCom Network News Page 7
Volume 6, Number 8 April 4, 1993
search for a treatment in Huntington's disease will be difficult because
the mechanism by which this gene causes the disease has not been
determined. The preliminary studies of the Huntington's gene indicate
that it is a gene which has not been previously studied. It does not
appear at present to be a member of any family of recognized genes and
may represent a new class of genes. Studies are now in progress to
determine:
1. In what tissues, organs or cell types is this gene
normally expressed?
2. At what stage of development is this gene normally
expressed?
3. What is the normal role of this gene?
4. How is the expression of this gene altered in people with
Huntington's disease?
It is hoped that methods to minimize and perhaps to halt the harmful
effects of the gone will be found. This will undoubtedly require an
intense scientific effort and will take considerable time.
The scientific community has worked very hard in finding the gone and the
process was long and tedious and required great patience and
perseverance. Hundreds of {*filter*} samples and brain specimens were
utilized in the research and the cooperation of the families with
affected members has been phenomenal. We can all take pride in the
cooperative effort that led to this discovery. Nevertheless, the job is
not over until an effective treatment is found. We need to continue to
work for funding and to continue the collaboration between families and
the scientific community.
Health InfoCom Network News Page 8
Volume 6, Number 8 April 4, 1993
Letter to Investigators on Availability of Taxol (2/93)
The following is the text of a letter sent on January 14, 1993 by the National
Cancer Institute's Drug Management and Authorization Section of the Cancer
Therapy Evaluation Program to all investigators using Taxol injection (NSC
125973) through the NCI's Division of Cancer Treatment.
Taxol has been approved by the U.S. cooking.net">food and Drug Administration (FDA) for the
treatment of metastatic carcinoma of the ovary. Therefore, the National Cancer
Institute (NCI) will discontinue the distribution of Taxol through the Group
C, Treatment Referral Center (TRC) Protocol for refractory ovarian cancer, and
Special Exception mechanism for any NEW patients on January 15, 1993. Supplies
of Taxol Injection are available commercially through pharmaceutical
wholesalers. Physicians wishing additional information on Taxol may contact
Bristol-Myers Squibb at 1-800-829-6587.
The National Cancer Institute, with the assistance and cooperation of the
manufacturer, Bristol-Myers Squibb, will continue to make Taxol available free
of charge to physicians for individual patients who started treatment under a
Group C, TRC or Special Exception Protocol. Additional drug for these
patients may be requested by completing a Clinical Drug Request form (NIH-986)
or by using the NCI's Electronic Ordering System. The protocol number and the
patient's first name and first initial of the last name must be indicated on
the request. Taxol for patients on the TRC protocols should be ordered as in
the past by protocol number.
Accrual of patients to the TRC protocol (TRC-9202), "Taxol in Patients with
Previously Treated Refractory {*filter*} Cancer" will continue through February
19, 1993. Information from this patient population is expected to provide
useful clinical information regarding the use of Taxol in the treatment of
{*filter*} cancer. After accrual is discontinued, these patients will continue to
receive Taxol at no cost as long as they continue to be treated on the
protocol.
Taxol, which is sent to you from DCT, NCI under the Group C, TRC and/or
Special Exception protocols, is still considered investigational since
treatment was initiated before FDA approval of the agent. Therefore, for
patients whose treatment was initiated under a Group C, TRC or Special
Exception protocol, we request that you take the following action so that we
may comply with FDA reporting regulations.
1. Adverse drug reactions must continue to be reported to
the Cancer Therapy Evaluation Program at 301-230-2330.
2. The "Report of Independent Investigator" is still
Health InfoCom Network News Page 9
Volume 6, Number 8 April 4, 1993
required at the conclusion of therapy for Special Exception
Protocols.
3. Continue to comply with the data reporting requirements
described in the Group C or TRC protocols.
Investigators with patients enrolled in NCI sponsored clinical trials other
than Group C, TRC or Special Exception protocols will continue to receive
clinical drug supplies from the NCI through standard ordering procedures.
Questions concerning Taxol should be directed to the Drug Management and
Authorization Section at 301-496-5725.
Health InfoCom Network News Page 10
Volume 6, Number 8 April 4, 1993
Taxol Approval Caps Years of Effort
The following is the text of a press release from the National Cancer
Institute, dated December 29, 1992.
Taxol (paclitaxel), a drug whose development was spearheaded by the National
Cancer Institute (NCI), has been approved by the U.S. cooking.net">food and Drug
Administration (FDA) for treating ovarian cancer that has failed other
therapy. The new drug will be marketed by Bristol-Myers Squibb Company.
Ovarian cancer is diagnosed in about 21,000 women in the United States each
year and claims 13,000 lives. Although most patients initially respond to
chemotherapy, the cancer often recurs in a form that is resistant to most
treatments.
"Taxol is a very important drug, and I am proud of NCI's role in bringing it
to the public," said NCI Director Samuel Broder, M.D. "The cooking.net">food and Drug
Administration and NCI's network of investigators have been exemplary in
collaborating to expedite development of this drug," he added. "Taxol is not
a cure, but it clearly can help many women with advanced ovarian cancer who
have few other options."
Broder also praised the Department of Agriculture's Forest Service, the
Department of the Interior's Bureau of Land Management, and Bristol-Myers
Squibb for their cooperation with NCI in developing an adequate supply of
taxol, which originally was scarce. These collaborations were made possible
by the Federal Technology Transfer Act of 1986, he noted.
History
Interest in taxol dates from the late 1960s, when a crude extract of bark from
the Pacific yew tree, Taxus brevifolia, which was being tested in a large-
scale NCI plant screening program, showed activity against cancer cells
growing in culture. In 1971, chemists at Research Triangle Institute in North
Carolina, working under an NCI contract, isolated the active component from
the extract and named it "taxol."
As additional quantities of the drug gradually became available, NCI was able
to evaluate it in animal tumor systems. Taxol proved active against a number
of these tumors, and the institute selected it in 1977 as a candidate for
clinical trials.
However, the sole source of taxol was Pacific yew bark, in which the
concentration of taxol is low. Obtaining bark and extracting taxol is costly
Health InfoCom Network News Page 11
Volume 6, Number 8 April 4, 1993
and time-consuming. These supply problems seriously impeded access to the
drug.
Mechanism of Action
In 1979, scientists at the Albert Einstein College of Medicine, whose work was
partially funded by NCI, reported that taxol had a novel effect on animal
cells. They found the drug acted to stabilize fiber-like structures called
microtubules that play a key role in the life cycle of cells. In the presence
of taxol, cells become clogged with bundles of microtubules and cease to grow
and divide.
This discovery, which suggested that taxol's way of attacking tumors was
unique, increased scientists' interest in studying the drug, and NCI
intensified its development efforts. Phase I trials were begun in 1983 under
the auspices of the institute's Division of Cancer Treatment. In 1985, Phase
II trials were undertaken, although their scope was limited because of the
restricted drug supply. [In Phase I clinical trials of a cancer drug, the
drug is given to a small number of patients, principally with the aims of
learning the best way to administer it and determining how much can be given
safely. Phase II trials are aimed at determining which tumor types the drug
may be active against. Phase III trials are large-scale trials designed to
establish whether or not the new agent is more effective than other therapies
against a specific type of cancer.]
In 1989, clinical investigators at The Johns Hopkins Oncology Center reported
that taxol produced partial or complete responses in 30 percent of previously
treated patients with advanced ovarian cancer. This surprisingly good result
created a stir among cancer researchers and greatly increased demand for the
scarce drug.
Collaborations
In order to increase supplies of taxol and bring it to market as quickly as
possible, NCI announced in August 1989 that it was holding an open competition
for a commercial partner to assist in taxol development. Bristol-Myers Squibb
was selected in December 1989 as a result of this competition. In 1990, as
more taxol became available, Phase III clinical trials began.
In January 1991, NCI and Bristol-Myers Squibb signed a Cooperative Research
and Development Agreement. The agreement stipulated that Bristol-Myers Squibb
would procure Pacific yew bark, supply formulated taxol to NCI, seek
alternative, renewable sources of the drug, and follow the necessary
procedures to obtain approval of taxol by the cooking.net">food and Drug Administration.
Health InfoCom Network News Page 12
Volume 6, Number 8 April 4, 1993
In return, NCI agreed to give the company exclusive access to its clinical and
pre-clinical data on taxol.
In 1991, NCI also initiated a series of agreements that enabled the Department
of Agriculture's Forest Service and the Department of the Interior's Bureau of
Land Management to cooperate with Bristol-Myers Squibb in procuring large
quantities of Pacific yew bark.
Increased Supply
Taxol supplies increased as a consequence of these agreements, enabling NCI to
make the drug available through a special program (Treatment Referral Center)
to certain patients with advanced ovarian cancer who were not eligible for
other clinical trials. Subsequently, as a result of additional information
suggesting that the drug was useful in {*filter*} cancer, the Treatment Referral
Center expanded its services to include patients with advanced {*filter*} cancer.
Bristol-Myers Squibb registered Taxol as a proprietary name in May 1992. Two
months later, the company filed a New Drug Application for Taxol with the FDA,
and in December, the FDA approved the drug for treatment of patients with
ovarian cancer which had failed previous chemotherapy.
Like most other cancer {*filter*}, taxol has certain side effects and can cause
unpleasant and sometimes dangerous toxicity. However, its risks are
outweighed by its potential benefits for certain patients with advanced
ovarian cancer.
Current Trials
Clinical data, some of which are preliminary, suggest that, in addition to its
proven usefulness in treating refractory (treatment-resistant) ovarian cancer,
taxol may prove helpful in treating {*filter*}, lung, and head and neck cancers.
The drug does not appear useful for patients with melanoma, or with colon,
prostate, renal, or cervical cancers.
Trials to determine whether taxol is effective in other cancer types are
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HICN608 Medical News Part 1/4