Public Teleconference Regarding Licensing and Collaborative Research Opportunities for: Use of CYP1B1*3 Genotyping To Predict Overall Survival in Patients With Prostate Cancer Prior to Treatment With Docetaxel; Dr. William D. Figg et al. (NCI), 24322-24324 [E7-8355]
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Federal Register / Vol. 72, No. 84 / Wednesday, May 2, 2007 / Notices
and personal information concerning
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invasion of personal privacy.
mmaher on DSK3CLS3C1PROD with $$_JOB
Name of Committee: National Institute of
Dental & Craniofacial Research Special
Emphasis Panel; 07–48, Review R25s.
Date: June 5, 2007.
Time: 2 p.m. to 3 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892 (Telephone Conference Call).
Contact Person: Sooyoun (Sonia) Kim, MS,
45 Center Dr, 4An 32B, Division of
Extramural Research, National Inst. of Dental
& Craniofacial Research, National Institutes
of Health, Bethesda, MD 20892, (301) 594–
4827, kims@email.nidr.nih.gov.
Name of Committee: National Institute of
Dental & Craniofacial Research Special
Emphasis Panel; 07–51, Review R21s PAR–
06–556.
Date: June 6, 2007.
Time: 1 p.m. to 4 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892 (Telephone Conference Call).
Contact Person: Lynn M. King, PhD,
Scientific Review Administrator, Scientific
Review Branch, 45 Center Dr., Rm 4AN–32F,
National Inst of Dental & Craniofacial
Research, National Institutes of Health,
Bethesda, MD 20892–6402, 301–594–5006,
lynn.king@nih.gov.
Name of Committee: National Institute of
Dental & Craniofacial Research Special
Emphasis Panel; 07–52, Review R21s.
Date: June 11, 2007.
Time: 12 p.m. to 3 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892 (Telephone Conference Call).
Contact Person: Lynn M. King, PhD,
Scientific Review Administrator, Scientific
Review Branch, 45 Center Dr., Rm 4AN–32F,
National Inst of Dental & Craniofacial
Research, National Institutes of Health,
Bethesda, MD 20892–6402, 301–594–5006,
lynn.king@nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.121, Oral Diseases and
Disorders Research, National Institutes of
Health, HHS)
Dated: April 25, 2007.
Jennifer Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 07–2149 Filed 5–1–07; 8:45 am]
BILLING CODE 4140–01–M
VerDate Mar 15 2010
03:08 Aug 19, 2011
Jkt 223001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of Diabetes and
Digestive and Kidney Diseases; Notice
of Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meeting.
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public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
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20036.
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Review Branch, DEA, NIDDK, National
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5452, (301) 594–7637, davilabloomm@extra.niddk.nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.847, Diabetes,
Endocrinology and Metabolic Research;
93.848, Digestive Diseases and Nutrition
Research; 93.849, Kidney Diseases, Urology
and Hematology Research, National Institutes
of Health, HHS)
Dated: April 25, 2007.
Jennifer Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 07–2150 Filed 5–1–07; 8:45 am]
BILLING CODE 4140–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
is hereby given of the following
meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Institute of
Allergy and Infectious Diseases Special
Emphasis Panel; Hematopoietic Cell
Transportation and Immune Tolerance.
Date: May 29, 2007.
Time: 1 p.m. to 4 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Rockledge 6700, 6700B Rockledge Drive,
Room 3136, Bethesda, MD 20817 (Telephone
Conference Call).
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and Transplantation Research; 93.856,
Microbiology and Infectious Diseases
Research, National Institutes of Health, HHS).
Dated: April 25, 2007.
Jennifer Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 07–2151 Filed 5–1–07; 8:45 am]
BILLING CODE 4140–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Public Teleconference Regarding
Licensing and Collaborative Research
Opportunities for: Use of CYP1B1*3
Genotyping To Predict Overall Survival
in Patients With Prostate Cancer Prior
to Treatment With Docetaxel; Dr.
William D. Figg et al. (NCI)
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
National Institutes of Health
National Institute of Allergy and
Infectious Diseases; Notice of Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
PO 00000
Frm 00059
Fmt 4703
Sfmt 4703
Technology Summary
The technology is an exciting
discovery in the field of prostate, breast
and lung cancer genetic markers having
profound clinical applications in
defining the optimal chemotherapeutic
E:\FEDREG\02MYN1.LOC
02MYN1
Federal Register / Vol. 72, No. 84 / Wednesday, May 2, 2007 / Notices
mmaher on DSK3CLS3C1PROD with $$_JOB
treatment schedule for each individual
patient. This genetic marker
(CYP1B1*3) can be potentially used as
a prognostic tool to predict survival rate
in patients prior to treatment, and to
asses their propensity to respond to
docetaxel treatment when being treated
not only for androgen-independent
prostate cancer (AIPC) but also for
breast cancer, lung cancer, stomach
cancer, head and neck cancer.
Description of Technology or Products
Prostate cancer develops most
frequently in men over fifty. Prostate
cancer is the most common type of
cancer in the United States, and it is
responsible for more male deaths than
any other cancer, except lung cancer.
The cancerous cells may spread
(metastasize) from the prostate to other
parts of the body, especially the bones
and lymph nodes.
Prostate cancer is most often
discovered by physical examination like
digital rectal examination or by
screening PSA level in blood. There is
some current concern about the
accuracy of the PSA test and its
usefulness. PSA levels can change due
to factors other than cancer. Two
common causes of high PSA levels are
enlargement of the prostate (benign
prostatic hyperplasia or BPH) and
infection in the prostate (prostatitis).
Screening for prostate cancer using PSA
is controversial because it is not clear if
the benefits of screening outweigh the
risks of follow-up diagnostic tests and
cancer treatments. However, prostate
cancer is typically confirmed by biopsy.
Further tests, such as X-rays and bone
scans, may be performed to determine
whether the cancer has spread.
Lung cancer is the most lethal of all
cancers worldwide, responsible for 1.2
million deaths annually. Non-small-cell
lung cancer (NSCLC) is the most
common lung cancer, accounting for
about 80% of all lung cancers.
Treatment for lung cancer involves
surgical removal of tumor,
chemotherapy, or radiation therapy,
combinations of these methods. The
treatment course depends on the
localization and the tumor metastasis as
well as the overall health status of the
patient. Docetaxel was the first drug
specifically approved by the FDA for the
second-line treatment of NSCLS.
Breast cancer is the second most fatal
form of cancer in females, affecting
approximately one out of thirty-nine in
the Western world after lung cancer.
The mainstay of breast cancer treatment
is surgery when the tumor is localized,
with possible adjuvant hormonal
therapy, chemotherapy, and/or
radiotherapy. Docetaxel is most
VerDate Mar 15 2010
03:08 Aug 19, 2011
Jkt 223001
commonly recommended for adjuvant
treatment (given with doxorubicin and
cyclophosphamide) as it has been
shown to be more successful in
advanced breast cancer patients than
paclitaxel, another drug approved by
FDA to treat advanced breast cancer.
Prostate cancer can be treated by
suppressing or blocking androgens with
surgery, radiation therapy, hormone
therapy, occasionally chemotherapy,
high intensity focused ultrasound
(HIFU), cryosurgery, or a combination of
these approaches. When prostate cells,
both healthy and cancerous, are
deprived of androgens, they no longer
proliferate and eventually die. Surgical
removal of the prostate, or
prostatectomy, is a common treatment
either for early stage prostate cancer or
for cancer which has failed to respond
to radiation therapy. Unfortunately,
prostate cancer usually returns within
about 18 months after anti-androgen
treatments. In such cases, the condition
is referred to as androgen-independent
(advanced and metastasized cancer)
prostate cancer (AIPC), and the tumors
are not responsive to anti-androgen
therapy. Currently, physicians
recommend chemotherapy for advanced
metastatic prostate cancers that have
failed to respond to other treatments.
However, treatment for AIPC is rapidly
evolving.
Chemotherapy with mitoxantrone and
prednisone offers a palliative benefit but
no survival advantage. Long-term
therapy with this regimen is not feasible
due to cumulative dose-related
cardiotoxicity. Single-agent docetaxel
treatment has shown to be very effective
in palliating metastatic prostate cancer
and is not associated with cumulative
dose-related toxicities. Currently,
Docetaxel is one of the most frequently
prescribed anti-cancer agents for the
treatment of certain forms of breast
cancer, lung cancer, stomach cancer,
head and neck cancer including AIPC.
Despite the relative success of docetaxel
in treating AIPC, high variability in
clinical response has been observed.
Due to variety of available treatment
options, choosing the most appropriate
treatment can be daunting. Since
prostate cancer is a disease of older men
who may be frail due to other health
issues, many patients die of other causes
before the prostate cancer can spread or
cause symptoms. Whether or not to treat
metastasized prostate cancer with
curative intent is a patient’s trade off
between the expected beneficial and
harmful effects in terms of survival time
and quality of life. A number of
important variables in each patient’s
history and previous pattern of response
must be addressed before choosing
PO 00000
Frm 00060
Fmt 4703
Sfmt 4703
24323
effective chemotherapy. Predicting
survival rate in patients prior to
treatment to asses their propensity to
response to docetaxel treatment is one
of the most important variables.
Cytochrome P450 (CYP1B1), upregulated in tumor cells, is involved in
the metabolism of steroid hormones,
metabolizing a variety of drugs, and
potentially important in prostate tumor
development and progression. Several
studies have evaluated the relationship
between CYP1B1 polymorphisms and
risk of various cancers including two
common single nucleotide
polymorphisms (SNP). These include
colorectal, lung, breast, ovarian, and
prostate cancers. The difference
between wild type and variant type
CYP1B1*3 is a single amino acid change
at position 432 of the expressed protein
caused by a single nucleotide change.
Recent studies have shown that this
polymorphism is associated with
increased risk of advanced prostate
cancer and altered drug metabolism. It
is known that docetaxel competitively
inhibits CYP1B1 mediated processes.
The responsiveness and overall survival
of patients with AIPC that are treated
with docetaxel, can be determined by
CYP1B1*3 genotype. In a study of 25
patients after docetaxel treatment, those
with AIPC that are homozygous or
heterozygous for the wild type
CYP1B1*3 exhibited increased (2x)
mean survival time compared to
homozygous variant. Additionally, there
was a similar difference in overall
survival observed in 20 men treated
with combination estramustine,
thalidomide, and docetaxel. Others have
found that the CYP1B1*3 allele was the
only SNP out of 8 studied variants
within 6 genes of known importance in
paclitaxel disposition to be associated
with lower progression free survival
following paclitaxel therapy in 93
patients with breast cancer. Knowledge
of an individual’s (multiple) phenotypic
profile will allow physicians to choose
the safest and most effective therapeutic
agent.
This technology has potential utility
as a prognostic tool to identify
individuals who may benefit from
therapy with docetaxel (i.e. patients that
are homozygous for the wild type
CYP1B1*3 or heterozygous).
Potential Market Size
Prostate cancer is the most common
cancer in America, affecting 1 in 6 men.
In 2007, more than 218,000 men will be
diagnosed with prostate cancer, and
more than 27,000 men will die from the
disease. In addition to the U.S.,
approximately 200,000 men in the EU
and 32,000 men in UK are diagnosed
E:\FEDREG\02MYN1.LOC
02MYN1
24324
Federal Register / Vol. 72, No. 84 / Wednesday, May 2, 2007 / Notices
patients with prostate cancer prior to
treatment with docetaxel. Genetic
markers with predictive power to assess
inter-subject differences resulting in
clinical outcome prior to docetaxel
administration have profound clinical
importance.
Current Competitive Product(s)
Currently there are no genetic markers
available to assess the responsiveness of
an AIPC-patient to therapy before
starting the treatment. Knowing
CYP1B1*3 genetic status saves time and
money of patients and prevents
ineffective treatments.
mmaher on DSK3CLS3C1PROD with $$_JOB
with prostate cancer each year and the
disease accounts for nearly one quarter
of all new cancer diagnoses of all new
male cancer diagnoses. Worldwide,
about 395,000 men are diagnosed with
prostate cancer each year and the
incidence is on the increase. The total
direct medical cost of prostate cancer in
the U.S. is $ 5 billion per year. It is
estimated that prostate cancer
therapeutics in the U.S., Europe and
Japan will cost $ 7.3 billion in 2011.
The global annual cancer market is
estimated at $35 billion with breast,
lung and prostate cancers being the
most significant contributors.
Incidences of lung, breast and stomach
cancers were found to be 351,344,
220,000, and 25,000 respectively in the
U.S. The current market size of drugs
used for the treatment of lung cancer is
$ 25 billion, while that of breast cancer
is $3.3 billion.
Next Step: Teleconference
Value Proposition
The FDA approved dose and schedule
for docetaxel in combination with
prednisone in the treatment of
androgen-independent (hormonerefractory) metastatic prostate cancer is
75 mg/m2 IV infusion for 1 hour every
3 weeks with 5 mg prednisone
continuously and average cost per cycle
of therapy is $ 4,298. The use of
docetaxel has been recently shown to
prolong survival and improve rates of
response and quality of life, but it is
unclear which patient would benefit
from treatment with this drug given that
high variability in clinical response has
been observed. A consequence of such
variability is that a docetaxal treatment
may be effective in one subject and
ineffective or poorly tolerated in another
subject. Thus, administration of such a
drug to a subject in whom the drug
would be ineffective would result in
wasted cost and time during which the
patient’s condition may significantly
worsen. Also, administration of a drug
to subject in whom the drug would not
be tolerated could result in a direct
worsening of the patient’s condition and
could even result in death. This
technology identifies the polymorphism
of CYP1B1*3 gene which modulates the
therapeutic response to docetaxel
treatment. This genetic marker can be
measured in DNA obtained from a blood
sample to predict overall survival in
VerDate Mar 15 2010
03:08 Aug 19, 2011
Jkt 223001
Intellectual Property Status
A PCT patent application was filed 09
September 2006.
Partnering Opportunity
Licensing opportunities are available.
In addition to licensing, the technology
is available for further development
through collaborative research
opportunities with the inventors.
Licensing Contact: Mojdeh Bahar;
(301) 435–2950; baharm@mail.nih.gov.
Collaborative Contact: John D. Hewes,
Ph.D.; (301) 435–3121;
hewesj@mail.nih.gov.
There will be a teleconference where
the principal investigator will explain
this technology. Licensing and
collaborative research opportunities will
also be discussed. If you are interested
in participating in this teleconference
please call or email Mojdeh Bahar; (301)
435–2950; baharm@mail.nih.gov. OTT
will then email you the date, time and
number for the teleconference.
Dated: April 25, 2007.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E7–8355 Filed 5–1–07; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HOUSING AND
URBAN DEVELOPMENT
[Docket No. FR–5121–N–14]
Notice of Proposed Information
Collection: Comment Request; Section
202 Supportive Housing for the Elderly
Application Submission Requirements
Office of the Assistant
Secretary for Housing—Federal Housing
Commissioner, HUD.
ACTION: Notice.
AGENCY:
SUMMARY: The proposed information
collection requirement described below
will be submitted to the Office of
Management and Budget (OMB) for
review, as required by the Paperwork
Reduction Act. The Department is
soliciting public comments on the
subject proposal.
DATES: Comments Due Date: July 2,
2007.
PO 00000
Frm 00061
Fmt 4703
Sfmt 4703
Interested persons are
invited to submit comments regarding
this proposal. Comments should refer to
the proposal by name and/or OMB
Control Number and should be sent to:
Lillian Deitzer, Reports Management
Officer, Department of Housing and
Urban Development, 451 7th Street,
SW., Room 4178, Washington, DC
20410, or Lillian—L—Deitzer@HUD.gov.
FOR FURTHER INFORMATION CONTACT:
Willie Spearmon, Director, Office of
Housing Assistance and Grant
Administration, Department of Housing
and Urban Development, 451 7th Street,
SW., Washington, DC 20410, telephone
(202) 708–3000 (this is not a toll free
number) for copies of the proposed
forms and other available information.
SUPPLEMENTARY INFORMATION: The
Department is submitting the proposed
information collection to OMB for
review, as required by the Paperwork
Reduction Act of 1995 (44 U.S.C.
Chapter 35, as amended).
This Notice is soliciting comments
from members of the public and affected
agencies concerning the proposed
collection of information to: (1) Evaluate
whether the proposed collection is
necessary for the proper performance of
the functions of the agency, including
whether the information will have
practical utility; (2) Evaluate the
accuracy of the agency’s estimate of the
burden of the proposed collection of
information; (3) Enhance the quality,
utility, and clarity of the information to
be collected; and (4) Minimize the
burden of the collection of information
on those who are to respond, including
the use of appropriate automated
collection techniques or other forms of
information technology, e.g., permitting
electronic submission of responses.
This Notice also lists the following
information:
Title of Proposal: Section 202
Supportive Housing for the Elderly
Application Submission Requirement.
OMB Control Number, if applicable:
2502–0267.
Description of the need for the
information and proposed use: The
collection of this information is
necessary to the Department to assist
HUD in determining applicant
eligibility and ability to develop
housing for the elderly within statutory
and program criteria. A thorough
evaluation of an applicant’s submission
is necessary to protect the Government’s
financial interest.
Agency form numbers, if applicable:
HUD–92015–CA, HUD–96010, HUD
92041, SF–424, SF–424–Supplemental,
SF–LLL, HUD–2880, HUD–2990, HUD–
2991, HUD–92042, HUD–96010, HUD
ADDRESSES:
E:\FEDREG\02MYN1.LOC
02MYN1
]]>Agencies
[Federal Register Volume 72, Number 84 (Wednesday, May 2, 2007)]
[Notices]
[Pages 24322-24324]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-8355]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Public Teleconference Regarding Licensing and Collaborative
Research Opportunities for: Use of CYP1B1*3 Genotyping To Predict
Overall Survival in Patients With Prostate Cancer Prior to Treatment
With Docetaxel; Dr. William D. Figg et al. (NCI)
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
Technology Summary
The technology is an exciting discovery in the field of prostate,
breast and lung cancer genetic markers having profound clinical
applications in defining the optimal chemotherapeutic
[[Page 24323]]
treatment schedule for each individual patient. This genetic marker
(CYP1B1*3) can be potentially used as a prognostic tool to predict
survival rate in patients prior to treatment, and to asses their
propensity to respond to docetaxel treatment when being treated not
only for androgen-independent prostate cancer (AIPC) but also for
breast cancer, lung cancer, stomach cancer, head and neck cancer.
Description of Technology or Products
Prostate cancer develops most frequently in men over fifty.
Prostate cancer is the most common type of cancer in the United States,
and it is responsible for more male deaths than any other cancer,
except lung cancer. The cancerous cells may spread (metastasize) from
the prostate to other parts of the body, especially the bones and lymph
nodes.
Prostate cancer is most often discovered by physical examination
like digital rectal examination or by screening PSA level in blood.
There is some current concern about the accuracy of the PSA test and
its usefulness. PSA levels can change due to factors other than cancer.
Two common causes of high PSA levels are enlargement of the prostate
(benign prostatic hyperplasia or BPH) and infection in the prostate
(prostatitis). Screening for prostate cancer using PSA is controversial
because it is not clear if the benefits of screening outweigh the risks
of follow-up diagnostic tests and cancer treatments. However, prostate
cancer is typically confirmed by biopsy. Further tests, such as X-rays
and bone scans, may be performed to determine whether the cancer has
spread.
Lung cancer is the most lethal of all cancers worldwide,
responsible for 1.2 million deaths annually. Non-small-cell lung cancer
(NSCLC) is the most common lung cancer, accounting for about 80% of all
lung cancers. Treatment for lung cancer involves surgical removal of
tumor, chemotherapy, or radiation therapy, combinations of these
methods. The treatment course depends on the localization and the tumor
metastasis as well as the overall health status of the patient.
Docetaxel was the first drug specifically approved by the FDA for the
second-line treatment of NSCLS.
Breast cancer is the second most fatal form of cancer in females,
affecting approximately one out of thirty-nine in the Western world
after lung cancer. The mainstay of breast cancer treatment is surgery
when the tumor is localized, with possible adjuvant hormonal therapy,
chemotherapy, and/or radiotherapy. Docetaxel is most commonly
recommended for adjuvant treatment (given with doxorubicin and
cyclophosphamide) as it has been shown to be more successful in
advanced breast cancer patients than paclitaxel, another drug approved
by FDA to treat advanced breast cancer.
Prostate cancer can be treated by suppressing or blocking androgens
with surgery, radiation therapy, hormone therapy, occasionally
chemotherapy, high intensity focused ultrasound (HIFU), cryosurgery, or
a combination of these approaches. When prostate cells, both healthy
and cancerous, are deprived of androgens, they no longer proliferate
and eventually die. Surgical removal of the prostate, or prostatectomy,
is a common treatment either for early stage prostate cancer or for
cancer which has failed to respond to radiation therapy. Unfortunately,
prostate cancer usually returns within about 18 months after anti-
androgen treatments. In such cases, the condition is referred to as
androgen-independent (advanced and metastasized cancer) prostate cancer
(AIPC), and the tumors are not responsive to anti-androgen therapy.
Currently, physicians recommend chemotherapy for advanced metastatic
prostate cancers that have failed to respond to other treatments.
However, treatment for AIPC is rapidly evolving.
Chemotherapy with mitoxantrone and prednisone offers a palliative
benefit but no survival advantage. Long-term therapy with this regimen
is not feasible due to cumulative dose-related cardiotoxicity. Single-
agent docetaxel treatment has shown to be very effective in palliating
metastatic prostate cancer and is not associated with cumulative dose-
related toxicities. Currently, Docetaxel is one of the most frequently
prescribed anti-cancer agents for the treatment of certain forms of
breast cancer, lung cancer, stomach cancer, head and neck cancer
including AIPC. Despite the relative success of docetaxel in treating
AIPC, high variability in clinical response has been observed. Due to
variety of available treatment options, choosing the most appropriate
treatment can be daunting. Since prostate cancer is a disease of older
men who may be frail due to other health issues, many patients die of
other causes before the prostate cancer can spread or cause symptoms.
Whether or not to treat metastasized prostate cancer with curative
intent is a patient's trade off between the expected beneficial and
harmful effects in terms of survival time and quality of life. A number
of important variables in each patient's history and previous pattern
of response must be addressed before choosing effective chemotherapy.
Predicting survival rate in patients prior to treatment to asses their
propensity to response to docetaxel treatment is one of the most
important variables.
Cytochrome P450 (CYP1B1), up-regulated in tumor cells, is involved
in the metabolism of steroid hormones, metabolizing a variety of drugs,
and potentially important in prostate tumor development and
progression. Several studies have evaluated the relationship between
CYP1B1 polymorphisms and risk of various cancers including two common
single nucleotide polymorphisms (SNP). These include colorectal, lung,
breast, ovarian, and prostate cancers. The difference between wild type
and variant type CYP1B1*3 is a single amino acid change at position 432
of the expressed protein caused by a single nucleotide change. Recent
studies have shown that this polymorphism is associated with increased
risk of advanced prostate cancer and altered drug metabolism. It is
known that docetaxel competitively inhibits CYP1B1 mediated processes.
The responsiveness and overall survival of patients with AIPC that are
treated with docetaxel, can be determined by CYP1B1*3 genotype. In a
study of 25 patients after docetaxel treatment, those with AIPC that
are homozygous or heterozygous for the wild type CYP1B1*3 exhibited
increased (2x) mean survival time compared to homozygous variant.
Additionally, there was a similar difference in overall survival
observed in 20 men treated with combination estramustine, thalidomide,
and docetaxel. Others have found that the CYP1B1*3 allele was the only
SNP out of 8 studied variants within 6 genes of known importance in
paclitaxel disposition to be associated with lower progression free
survival following paclitaxel therapy in 93 patients with breast
cancer. Knowledge of an individual's (multiple) phenotypic profile will
allow physicians to choose the safest and most effective therapeutic
agent.
This technology has potential utility as a prognostic tool to
identify individuals who may benefit from therapy with docetaxel (i.e.
patients that are homozygous for the wild type CYP1B1*3 or
heterozygous).
Potential Market Size
Prostate cancer is the most common cancer in America, affecting 1
in 6 men. In 2007, more than 218,000 men will be diagnosed with
prostate cancer, and more than 27,000 men will die from the disease. In
addition to the U.S., approximately 200,000 men in the EU and 32,000
men in UK are diagnosed
[[Page 24324]]
with prostate cancer each year and the disease accounts for nearly one
quarter of all new cancer diagnoses of all new male cancer diagnoses.
Worldwide, about 395,000 men are diagnosed with prostate cancer each
year and the incidence is on the increase. The total direct medical
cost of prostate cancer in the U.S. is $ 5 billion per year. It is
estimated that prostate cancer therapeutics in the U.S., Europe and
Japan will cost $ 7.3 billion in 2011.
The global annual cancer market is estimated at $35 billion with
breast, lung and prostate cancers being the most significant
contributors. Incidences of lung, breast and stomach cancers were found
to be 351,344, 220,000, and 25,000 respectively in the U.S. The current
market size of drugs used for the treatment of lung cancer is $ 25
billion, while that of breast cancer is $3.3 billion.
Current Competitive Product(s)
Currently there are no genetic markers available to assess the
responsiveness of an AIPC-patient to therapy before starting the
treatment. Knowing CYP1B1*3 genetic status saves time and money of
patients and prevents ineffective treatments.
Value Proposition
The FDA approved dose and schedule for docetaxel in combination
with prednisone in the treatment of androgen-independent (hormone-
refractory) metastatic prostate cancer is 75 mg/m2 IV
infusion for 1 hour every 3 weeks with 5 mg prednisone continuously and
average cost per cycle of therapy is $ 4,298. The use of docetaxel has
been recently shown to prolong survival and improve rates of response
and quality of life, but it is unclear which patient would benefit from
treatment with this drug given that high variability in clinical
response has been observed. A consequence of such variability is that a
docetaxal treatment may be effective in one subject and ineffective or
poorly tolerated in another subject. Thus, administration of such a
drug to a subject in whom the drug would be ineffective would result in
wasted cost and time during which the patient's condition may
significantly worsen. Also, administration of a drug to subject in whom
the drug would not be tolerated could result in a direct worsening of
the patient's condition and could even result in death. This technology
identifies the polymorphism of CYP1B1*3 gene which modulates the
therapeutic response to docetaxel treatment. This genetic marker can be
measured in DNA obtained from a blood sample to predict overall
survival in patients with prostate cancer prior to treatment with
docetaxel. Genetic markers with predictive power to assess inter-
subject differences resulting in clinical outcome prior to docetaxel
administration have profound clinical importance.
Intellectual Property Status
A PCT patent application was filed 09 September 2006.
Partnering Opportunity
Licensing opportunities are available. In addition to licensing,
the technology is available for further development through
collaborative research opportunities with the inventors.
Licensing Contact: Mojdeh Bahar; (301) 435-2950;
baharm@mail.nih.gov.
Collaborative Contact: John D. Hewes, Ph.D.; (301) 435-3121;
hewesj@mail.nih.gov.
Next Step: Teleconference
There will be a teleconference where the principal investigator
will explain this technology. Licensing and collaborative research
opportunities will also be discussed. If you are interested in
participating in this teleconference please call or email Mojdeh Bahar;
(301) 435-2950; baharm@mail.nih.gov. OTT will then email you the date,
time and number for the teleconference.
Dated: April 25, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-8355 Filed 5-1-07; 8:45 am]
BILLING CODE 4140-01-P
