■PDQ Cancer Treatment Information Summaries Health Professionals
PDQ® Treatment Health Professionals
Important: This information is intended for use by doctors and other health care professionals.
If you are a cancer patient, your doctor can explain how
it applies to you, or you can call the Cancer Information Service at
1-800-422-6237.
Bladder cancer Table of Contents
GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
TREATMENT OPTION OVERVIEW
STAGE 0 BLADDER CANCER
Tis or Ta, N0, M0
STAGE I BLADDER CANCER
T1, N0, M0
STAGE II BLADDER CANCER
T2a, N0, M0 or T2b, N0, M0
STAGE III BLADDER CANCER
T3a, N0, M0 or T3b, N0, M0 or T4a, N0, M0
STAGE IV BLADDER CANCER
T4b, N0, M0, any T, N1-N3, M0, or any T, any N, M1
RECURRENT BLADDER CANCER
● GENERAL INFORMATION
Approximately 70%-80% of patients with newly diagnosed bladder cancer will
present with superficial bladder tumors (i.e., stage Ta, Tis, or T1). Those
who do present with superficial, noninvasive bladder cancer are often curable,
and those with deeply invasive disease can sometimes be cured by surgery,
irradiation, or a combination of modalities that include chemotherapy. Studies
have demonstrated that some patients with distant metastases have achieved
long-term complete response following treatment with combination chemotherapy
regimens. There are clinical trials suitable for patients with all stages of
bladder cancer; whenever possible, patients should be included in clinical
trials designed to improve on standard therapy.
The major prognostic factors in carcinoma of the bladder are the depth of
invasion into the bladder wall and the degree of differentiation of the tumor.
Most superficial tumors are well differentiated. Patients in whom superficial
tumors are less differentiated, large, multiple, or associated with carcinoma
in situ (Tis) in other areas of the bladder mucosa are at greatest risk for
recurrence and the development of invasive cancer. Such patients may be
considered to have the entire urothelial surface at risk for the development of
cancer. Tis may exist for variable durations. Adverse prognostic features
associated with a greater risk of disease progression include the presence of
multiple aneuploid cell lines, nuclear p53 overexpression, and expression of
the Lewis-x blood group antigen.[1-3] Patients with Tis who have a complete
response to BCG (bacillus Calmette-Guerin) have approximately a 20% risk of
disease progression at 5 years; patients with incomplete response have
approximately a 95% risk of disease progression.[1] Several treatment methods
(i.e., transurethral surgery, intravesical medications, and cystectomy) have
been used in the management of patients with superficial tumors, and each
method can be associated with 5-year survival in 55%-80% of patients
treated.[1,2]
Invasive tumors that are confined to the bladder muscle on pathologic staging
after radical cystectomy are associated with approximately a 75% 5-year
progression-free survival rate. Patients with more deeply invasive tumors
(which are also usually less well differentiated) experience 5-year survival
rates of 20%-40% following radical cystectomy. When the patient presents with
locally extensive tumor that invades pelvic viscera or with metastases to lymph
nodes or distant sites, 5-year survival is uncommon, but considerable
symptomatic palliation can still be achieved.[4]
Expression of the tumor suppressor gene p53 also has been associated with an
adverse prognosis for patients with invasive bladder cancer. A retrospective
study of 243 patients treated by radical cystectomy found that the presence of
nuclear p53 was an independent predictor for recurrence among patients with
stage T1, T2, or T3 tumors.[5] Another retrospective study showed p53
expression to be of prognostic value when considered with stage or labeling
index.[6]
The survival of 111 patients with invasive bladder cancer who were treated with
initial M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin)
chemotherapy followed by surgery was analyzed for pretreatment prognostic
factors. Multivariate analysis revealed that independent variables associated
with poor survival included expression of p53, age, tumor multifocality,
presence of palpable mass, and initial tumor stage.[7,8]［以下略］
■Bladder cancer - PDQ® Treatment Patients -Cancer Information Summaries
■PDQ® . Treatment . Patients［米国国立癌研：膀胱癌治療ガイドライン］患者向け
Bladder cancer Table of Contents
OVERVIEW OF PDQ
What is PDQ?
How to use PDQ
DESCRIPTION
What is cancer of the bladder?
STAGE EXPLANATION
Stages of cancer of the bladder
Stage 0 or carcinoma in situ
Stage I
Stage II
Stage III
Stage IV
Recurrent
TREATMENT OPTION OVERVIEW
How cancer of the bladder is treated
Treatment by stage
STAGE 0 BLADDER CANCER
STAGE I BLADDER CANCER
STAGE II BLADDER CANCER
STAGE III BLADDER CANCER
STAGE IV BLADDER CANCER
RECURRENT BLADDER CANCER
TO LEARN MORE
［略］
● TREATMENT OPTION OVERVIEW
● How cancer of the bladder is treated
There are treatments for all patients with cancer of the bladder. Four kinds
of treatment are used:
surgery (taking out the cancer in an operation)
radiation therapy (using high-dose x-rays or other high-energy rays to kill
cancer cells and shrink tumors)
chemotherapy (using drugs to kill cancer cells)
biological therapy (using the body's immune system to fight cancer)
A new type of treatment called photodynamic therapy is being tested in clinical
trials.
Surgery is a common treatment of cancer of the bladder. A doctor may take out
the cancer using one of the following operations:
Transurethral resection is an operation that uses a cystoscope inserted into
the bladder through the urethra. The doctor then uses a tool with a small
wire loop on the end to remove the cancer or to burn the tumor away with
high-energy electricity (fulguration).
Segmental cystectomy is an operation to take out the part of the bladder
where the cancer is found. Because bladder cancer often occurs in more than
one part of the bladder, this operation is used only in selected cases where
the cancer is in one area.
Cystectomy is an operation to take out the bladder.
Radical cystectomy is an operation to take out the bladder and the tissue
around it. In women, the uterus, ovaries, fallopian tubes, part of the
vagina, and urethra are also removed. In men, the prostate and the glands
that produce fluid that is part of the semen (seminal vesicles) are also
removed, and the urethra may be removed as well. The lymph nodes in the
pelvis may also be taken out (pelvic lymph node dissection).
Urinary diversion is an operation to make a way for urine to pass out of the
body so that it does not go through the bladder. It is used to relieve
bladder symptoms when the tumor has spread.
If the bladder is removed, a doctor will need to make a new way for the body to
store and pass urine. There are several ways to do this. Sometimes a doctor
will use part of the small intestine to make a tube through which urine can
pass out of the body through an opening (stoma) on the outside of the body.
This procedure is sometimes called an ostomy or urostomy.
If a patient has an ostomy, a special bag to collect urine will need to worn.
This special bag, which sticks to the skin around the stoma with a special
glue, can be thrown away after it is used. The bag does not show under
clothing and most people take care of these bags themselves. The doctor may
also use part of the small intestine to make a new storage pouch (a continent
reservoir) inside the body where urine can collect. A patient would then need
to use a tube (catheter) to drain the urine through the stoma. Newer methods
use a part of the small intestine to make a new storage pouch that is connected
to the remaining part of the urethra if it has not been removed. Urine then
passes out of the body through the urethra, and a stoma is not necessary.
Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy may be
taken by pill, or it may be put in the body through a needle inserted into a
vein or muscle. Chemotherapy is called a systemic treatment because the drug
enters the bloodstream, travels through the body, and can kill cancer cells
outside the bladder. Chemotherapy may also be given in a fluid that is put
into the bladder through a tube going through the urethra (intravesical
chemotherapy).
If a doctor removes all the cancer that can be seen at the time of the
operation, a patient may be given chemotherapy after surgery to kill any cancer
cells that are left. Chemotherapy given after an operation to a person who has
no cancer cells that can be seen is called adjuvant chemotherapy. For bladder
cancer, chemotherapy is sometimes given before surgery to try to improve
results or to preserve the bladder. Chemotherapy given in this manner is
called neoadjuvant chemotherapy. Neoadjuvant chemotherapy is being carefully
studied in a clinical trial sponsored by the National Cancer Institute.
Radiation therapy uses high-energy x-rays to kill cancer cells and shrink
tumors. Radiation may come from a machine outside the body (external radiation
therapy) or from putting materials that produce radiation (radioisotopes)
through thin plastic tubes in the area where the cancer cells are found
(internal radiation therapy).
Biological therapy tries to get the body to fight cancer. It uses materials
made by the body or made in a laboratory to boost, direct, or restore the
body's natural defenses against disease. Biological therapy is sometimes
called biological response modifier (BRM) therapy or immunotherapy. Biological
therapy may be given in a fluid that is put into the bladder through a tube
going through the urethra (intravesical biological therapy).
Photodynamic therapy is a new type of treatment that uses special drugs and
light to kill cancer cells. A drug that makes cancer cells more sensitive to
light is put into the bladder, and a special light is used to shine on the
bladder. This therapy is being studied for early stages of bladder cancer.
［以下略］
Contents of this page:
From the NIH
General/Overviews
Anatomy/Physiology
Clinical Trials
Diagnosis/Symptoms
Disease Management
Prevention/Screening
Research
Specific Conditions/Aspects
Treatment
Dictionaries/Glossaries
Organizations
Statistics
The primary NIH organization for research on Bladder Cancer is the
National Cancer Institute
Search MEDLINE for recent research articles on
・ Bladder Cancer
You may also be interested in these MEDLINEplus related pages:
・ Bladder Diseases
・ Cancers
・ Kidneys and Urinary System
●From the National Institutes of Health
What You Need to Know About Bladder Cancer (National Cancer Institute)
●General/Overviews
What is Bladder Cancer? (Mayo Foundation for Medical Education and Research)
What is Bladder Cancer? (American Cancer Society)
●Anatomy/Physiology
Kidneys and Urinary Tract (Nemours Foundation)
●Clinical Trials
ClinicalTrials.gov: Bladder Neoplasms (National Institutes of Health)
ClinicalTrials.gov: Urethral Neoplasms (National Institutes of Health)
●Diagnosis/Symptoms
Can Bladder Cancer Be Found Early? (American Cancer Society)
Cystoscopy (Patient Education Institute) - requires Flash plug-in
Cystoscopy and Ureteroscopy (National Institute of Diabetes and Digestive and Kidney Diseases)
Hematuria: Blood in the Urine (National Institute of Diabetes and Digestive and Kidney Diseases)
How Is Bladder Cancer Diagnosed? (American Cancer Society)
How Is Bladder Cancer Staged? (American Cancer Society)
●Disease Management
Bladder Cancer: What Happens After Treatment? (American Cancer Society)
●Prevention/Screening
Bladder Cancer (PDQ): Screening (National Cancer Institute)
Bladder Cancer Questionnaire (Harvard Center for Cancer Prevention)
Can Bladder Cancer Be Prevented? (American Cancer Society)
What are the Risk Factors for Bladder Cancer? (American Cancer Society)
●Research
Bladder Cancer Recurrence Held at Bay With Improved Drug Delivery (American Cancer Society)
Researchers Confirm Smoking Increases Risk of Bladder Cancer (American Cancer Society)
Study Finds Possible Link Between Hair Dye and Bladder Cancer (American Cancer Society)
Treatment to Prevent Bladder Cancer Return Is Improving (American Cancer Society)
What's New in Bladder Cancer Research and Treatment? (American Cancer Society)
●Specific Conditions/Aspects
Do We Know What Causes Bladder Cancer? (American Cancer Society)
What Should You Ask Your Doctor About Bladder Cancer? (American Cancer Society)
●Treatment
Biological Therapies: Using the Immune System to Treat Cancer (National Cancer Institute)
Also available in: Spanish
Bladder Cancer (PDQ): Treatment (National Cancer Institute)
Also available in: Spanish
Transitional Cell Cancer of the Renal Pelvis and Ureter (PDQ): Treatment (National Cancer Institute)
Also available in: Spanish
Urethral Cancer (PDQ): Treatment (National Cancer Institute)
Also available in: Spanish
Urinary Cystectomy (Animation Education Group)
●Dictionaries/Glossaries
Bladder Cancer: Glossary (American Foundation for Urologic Disease)
Urologic Diseases Dictionary (National Institute of Diabetes and Digestive and Kidney Diseases)
●Organizations
American Cancer Society
American Foundation for Urologic Disease
Directory of Kidney and Urologic Diseases Organizations (National Kidney and Urologic Diseases Information Clearinghouse)
National Cancer Institute
●Statistics
Urinary Bladder: U.S. Racial/Ethnic Cancer Patterns (National Cancer Institute)
What Are the Key Statistics for Bladder Cancer? (American Cancer Society)
Page last updated: 13 November 2002
Topic last reviewed: 31 July 2002
www.medwebplus.com
★Broader terms: -
★Related terms: - Gynecology - Obstetrics - Orthopedics - Surgery - Thoracic Surgery -
★Narrower terms: -
★Focussed subsets for Urology: - Almanacs -Congresses -Diabetes -Educational resources -Endocrinology -Government Agencies -Gynecology -
Incontinence -Internship and Residency -Lists of Internet Resources -Medical Oncology -Neoplasms -Nursing -
Organizations -Patient Education -Periodicals -Professional Practice -Reproductive Medicine -Societies -Societies, Scientific -Tutorials -Urogenital Diseases -ACTA UROLOGICA BELGICA (table of contents of current issue)
GO American Foundation for Urologic Disease
GO American Society of Andrology
GO Search for Accredited Urology Residency Training Programs
GO ANNALES D UROLOGIE (tables of contents)
GO Braun Fertility
GO British journal of urology: journal of the British Association of Urological Surgeons and the European Society of Paediatric Urology (tables of contents)
GO Circumcision Information and Resource Pages
GO Clinique d'urologie du Haut-Richelieu
GO Complete Urology, Andrology & Male Infertility InfoBase maintained by Giannis Zoumpos
GO Current opinion in urology on BioMedNet (tables of contents, abstracts, full text articles -- requires free id and password)
GO Digital urology journal
GO Digital urology journal / Urology nurses online Calendar.
Pages: 12 3 4 5
-------------------------------
GO ANTI-CANCER DRUGS (general information)
Journal of Urologyｮ
Techniques in Urology / 1079-3259 / Journal
★Urology オンライン雑誌集
Clinical Autonomic Research / 0959-9851 / Journal
Current Opinion in Urology / 0963-0643 / Journal
Journal of Vascular and Interventional Radiology / 1051-0443 / Journal
Sexually Transmitted Diseases / 0148-5717 / Journal
Techniques in Urology / 1079-3259 / Journal
[]Hexaminolevulinate (Hexvix [Photocure ASA])
| []●製品 Hexaminolevulinate (Hexvix [Photocure ASA]) |
日本語版註）Hexaminolevulinate (Hexvix [Photocure ASA])
【別名】 【開発元】Photocure ASA[NO] [DBR_ID]
【化学名】
【承認】FDA申請=2005.6.30、FDA承認=x ; 【EU】Hexvix[PhotoCure ASA]スエーデン申請2002.12.18承認2004.9.20、EU/EEA26ヵ国に相互承認申請2004.12.1承認2005.3.2 Nordic諸国を除く全世界の開発販売権をGE Healthcareにライセンス 【製剤〜EU】Pack of one 10 ml glass vial containing 85 mg of hexaminolevulinate as 100 mg hexaminolevulinate hydrochloride as a powder and one 50 ml polypropylene or glass vial containing solvent. After reconstitution in 50 ml of solvent, 1 ml of the solution contains 1.7 mg hexaminolevulinate which corresponds to a 8 mmol/l solution of hexaminolevulinate. 【適応〜EU】for the detection of bladder cancer in patients with known or suspected bladder cancer 【用法用量〜EU】成人：8 mmol/lで50mlをカテーテル経由で膀胱内に注入、６０分保持。 液排出に引き続きblue light (wavelength 380--450 nm) fluorescence cystoscopy(青色灯を用いた 蛍光膀胱鏡検査)を６０分以内に開始。 【作用】 【特徴】the first product on the market that improves cystoscopic diagnosis of bladder cancer. 【製品情報〜EU】www.hexvix.com 【添付文書〜EU】Hexvix Prescribing Information 【日本】未開発 【その他】UK Price £286
- http://www.photocure.com/
- Oslo Stock Exchange (PHO)上場.
photodynamic technology, targeting key dermatology and oncology markets.
1993 創業
1997 従業員雇用開始 Metvix臨床研究開始
2000 Metvixが初の販売承認申請
2001 Metvix初承認。 MetvixをGaldermaにライセンス
2002 Hexvixが初の販売承認申請
2003 Galderma's first Metvix launch
2004 Hexvix初承認
2005 Hexvixが全EU/EEA諸国で承認、Nordic地域で発売、米国申請
2006 HexvixをGE Healthcareヘライセンス。 HexvixがEU発売
●会社決算
| (NOK 000) | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 備考 |
| 売上収入 | 61,667 | 38,007 | 36,855 | 23,380 | 10,892 | |
| Milestone収入 | 148,653 | 15,634 | 40,954 | 31,774 | 14,331 | |
| 総収入 | 210,320 | 53,641 | 77,809 | 55,154 | 25,223 | |
| 売上原価 | 22,251 | 13,430 | 13,066 | 9,514 | 5,832 | |
| 粗利益 | 188,070 | 40,211 | 64,743 | 45,640 | 19,391 | |
| 営業利益 | 78,342 | (47,251) | (40,861) | (53,655) | (109,526) | |
| 経常利益 | 84,730 | (-38,474) | (45,322) | | | |
| 当期純利益 | 85,082 | (38,210) | (45,032) | | | |
| 研究開発費 | 38,200 | 38,238 | 31,718 | 38,377 | 77,300 | |
| 従業員数[連結] | | | | | | |
|
| 製品売上高/product split |
| Metvix/Aktilite | 51,554 | 36,396 | | | | | [] |
| Hexvix | 10,113 | 1,411 | | | | | [] |
| その他 | - | 200 | | | | | [] |
| 合計 | 61,667 | 38,007 | | | | | [] |
| | | | | | |
●Products
★Metvix(methyl aminolevulinate) actinic keratosis(AK) /non-melanoma skin cancer
(superficial and nodular basal cell carcinoma(BCC)
- MetvixR photodynamic therapy (MAL-PDT)
★Hexvix(hexaminolevulinate) 膀胱癌診断
●R&D
●Investors
★Annual Report 2006[pdf,29p;2007.4.16]
●Press/Media - Press Release
Photocure - Metvixia(TM) NDA submitted to FDA[2007.6.28]
Approval for Hexvix obtained in Italy[2007.6.19]
Price approval and reimbursement for Hexvix obtained in France [2007.5.30]
Forth quarter report 2006[2007.2.28]
US option for Hexvix exercised by GE Healthcare[2006.7.31]
PhotoCure - GE Healthcare has 60 days to exercise US option for Hexvix(R)[2006.5.31]
FDA requests more information related to Hexvix(R) NDA[2006.4.20]
PhotoCure and GE Healthcare introduce Hexvix in Europe[2006.4.7]
Metvix(R) approved for Bowen's in 22 European countries[2005.11.25]
Hexvix(R) NDA submitted to FDA[2005.6.30]
PhotoCure and Galderma free to market Metvix(R) in Australia[2005.4.6]
Hexvix(R) approved in 26 European countries [2005.3.2] - EU/EEA26ヵ国相互承認2005.3.2
2004.12.03★FDA Review of Metvix(R) for the treatment of skin cancer
2004.12.01★Hexvix(R) marketing application found fileable in 26 European countries - EU/EEA26ヵ国に相互承認申請2004.12.1
2004.11.29★Metvix(R) approved in 8 new European countries
2004.09.23★Hexvix(R) application in EU / EEA countries to be filed later this year
2004.09.20★Marketing approval for Hexvix(R) - スエーデン承認2004.9.20
2004.07.28★Regulatory Approval of Metvix(R) in the US
2004.06.17★US New Drug Application approval expected for Metvix
2004.05.27★Galderma initiates new Metvix(R) launches
2003.11.25★Metvix(R) progresses
2003.09.25★Hexvix(R) imaging one step closer to commercialisation
2003.09.11★FDA Advisory Committee Reviews Metvix(R) for the treatment of skin cancer
2003.08.08★Progress in FDA's evaluation of Metvix(R) application
2003.06.17★New approval for Metvix(R) in Australia
2003.05.09★Galderma initiates Metvix(R) PDT UK launch activities
2003.04.02★Positive Metvix(R) PDT results
2003.04.02★Metvix(R) PDT approved in Australia
2003.03.28★Hexvix(R) improves treatment of bladder cancer patients
2003.02.24★Marketing Application for Metvix(R) PDT in Australia Recommended for Approval
2003.02.18★New NDA for Metvix(R) PDT Submitted to FDA
2003.02.06★Metvix(R) PDT Launched in Germany
2002.12.18★PhotoCure Files First MAA for Hexvix(R) Cystoscopy -スエーデン申請2002.12.18
2002.09.23★Metvix(R) PDT approvable in the US
2002.09.03★Positive Phase III Clinical Results for Hexvix(R)
2002.08.19★High Clinical Acceptance of Metvix(R)PDT
2002.05.23★National Marketing Authorisation for Metvix(R) PDT issued in Finland
2002.05.07★Commercialisation of Metvix(R)PDT in Europe on track
2002.03.06★National Marketing Authorisation for Metvix(R) PDT issued in Germany
2002.02.12★Long-term Phase III Study with Metvix(R) for BCC
2002.02.08★PhotoCure Receives Marketing Approval for Metvix(R) PDT in New Zealand
2002.02.01★Metvix(R) PDT approved in Norway
2002.01.15★Metvix(R) application Switzerland
●Hexaminolevulinate Product (Hexvix) to Improve Photodetection of Bladder Cancer in Italy[Medscape July 30, 2007]
On June 19, a hexaminolevulinate (HAL) product (Hexvix, PhotoCure ASA, and marke
ted by GE Healthcare) received marketing and price approvals in Italy.
The HAL product previously was approved in March 2005 by the European Commission
for use in 25 countries, 2 of which (Spain and France) have also granted marketing approval.
[]
| [1049]●製品：膀胱癌治療薬バルルビシン［バルスター］ valrubucin [Valstar] |
日本語版註）膀胱癌治療薬バルルビシン［バルスター］ valrubucin [Valstar]
【別名】 【開発元】Anthra Pharmaceuticals, Inc.(2002事業廃止) [DBR_ID]
【化学名】
【承認】FDA申請=Dec 30, 1997、FDA承認=25-SEP-98[Anthra Pharmaceuticals] 発売:1-1999 ;販売元Medeva社 販売中止2002Q2→2006.4 Valera Pharmaceuticals, Inc.が権利買収→2007.4.18 Indevus Pharmaceuticals, Inc.がValera社を買収。 Indevus社は再申請2007.4.19→Approvable Letter 2007.8.17 【製剤】 【適応】For intravesical therapy of BCG-refractory carcinoma in situ(CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality 【用法用量】
【作用】 【特徴】唯一のBCG不応性膀胱癌治療薬 【製品情報】 【添付文書】http://www.fda.gov/cder/foi/label/1998/20892lbl.pdf 【EU】未開発 【日本】未開発 【その他】
註2)Anthra Pharmaceuticals, Inc.は従業員33人の制癌剤に特化した開発ベンチャー。 Valstarは米国ではMedeva社を販売元とした。 又同社は高カルシウム血症治療薬Bonefosの米国内開発・販売権を独シェーリング社から獲得。 企業データは●Anthra Pharmaceuticals, Inc. - Hoover's Company Capsuleからも入手可。 同様にhttp://www.medeva.co.uk - Medeva's Home Page; Medeva PLC - Hoover's Company Capsule［英国メデバ社］1997売上$587百万＄［約734億円］。 フーバー企業カプセル（13000社の無料企業情報）に関しては吉川 徹（吉川医薬研）氏にご教示いただいた。
●2004.5.1 以降 Drugs@FDA
Drug Name(s) =VALSTAR PRESERVATIVE FREE (VALRUBICIN)
FDA Application No. =(NDA) 020892
Active Ingredient(s)=VALRUBICIN
Company =INDEVUS PHARMS
Dosage Form/Route =SOLUTION; INTRAVESICAL 40MG/ML
Strength =
- Approval Date=09/25/1998[000] :Label[添付文書]|Letter[承認書]|Review
Original Approval or Tentative Approval Date September 25, 1998
Chemical Type 1 New molecular entity (NME)
Review Classification P Priority review drug/O Orphan drug
情報ソースFDA Drug Approvals List August 1998
Date: 2 Nov 1998, Size 29.5K, http://www.fda.gov/cder/da/da0998.htm
Original Application #: 020892
Approval Date: 25-SEP-98
Trade Name: VALSTAR
Chemical Type: 1
Therapeutic Potential: P
Dosage Form: SOLUTION
Applicant: ANTHRA PHARMACEUTICALS INC
Active Ingredient(s): VALRUBICIN
OTC/RX Status: RX
Indication(s): For intravesical therapy of BCG-refractory carcinoma in situ(CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality
情報ソース● 16-Mar-1999 04:01:52 pm, Drug Approvals Part 2
Valstar (valrubicin) Sterile Solution for Intravesical Instillation, 5 mL, Single-Use Vials (40 mg/mL)
Anthra Pharmaceuticals
NDA 20-892
9/25/98
9/28［承認書］
9/28[医薬品添付文書]
Valstar Indication: intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality.
Application Number: 020892
Active Ingredient : VALRUBICIN
Proprietary Name : VALSTAR PRESERVATIVE FREE [INDEVUS PHARMS] SOLUTION; INTRAVESICAL 40MG/ML
Approval Date : Sep 25, 1998
Exclusivity Data : -
Patent Data : -
Brand Name: Valstar
Active Ingredient: valrubicin
Strength(s): 40mg/ml
Dosage Form(s): Intravesical Sterile Solution
Company Name: Anthra Pharmaceuticals
Availability: Prescription only, hospital use only
*Date Approved by the FDA: September 25, 1998
*Approval by FDA does not mean that the drug is available for consumers at this time.
●What is Valstar used for?
Valstar is used for treatment of patients with BCG-resistant cancer of the urinary bladder for whom surgical removal of the bladder is not safe. Treatment with Valstar is through drug instillation into the urinary bladder.
●Who
should not be treated with Valstar?
You should not be given Valstar if you have any of the following conditions:
・Known reaction to other drugs that are similar to Valstar or Cremophorｮ EL
・Urinary tract infection at the time of treatment
・Small bladder capacity (i.e., unable to tolerate a 75ml instillation)
●Special Warning(s) with Valstar:
Valstar has been shown to bring about temporary disappearance of cancer in only about 1 in 5 patients with treatment-resistant bladder cancer. Delaying surgical removal of all or part of the bladder could lead to the spread of bladder cancer, which is deadly. The risk of bladder cancer spreading to other parts of the body from the delay of needed surgery may be difficult to determine but will increase the longer it is delayed.
Your doctor will evaluate and monitor your response to treatment with Valstar to decide whether surgery should be reconsidered.
Certain conditions of the bladder may delay or prevent treatment with Valstar. Your doctor will evaluate you to determine if you are a candidate for treatment with Valstar.
●General Precautions with Valstar:
You should discuss with your doctor the risks involved with delaying surgery, which could lead to bladder cancer spreading to other parts of your body (See Special Warnings).
Side effects from treatment with Valstar mainly involve irritable bladder symptoms (e.g., bladder spasm, spontaneous discharge of Valstar) occurring during treatment with Valstar or shortly after treatment. For the first 24 hours after treatment with Valstar, most patients have red-colored urine.
Tell your doctor immediately if you experience any continued irritable bladder symptoms or if you have red-colored urine after the first 24 hours following treatment.
Men and women of childbearing age should use an effective birth control method during the Valstar treatment period.
Women: Tell your doctor if you are trying to become pregnant, are already pregnant, or are breast-feeding. You should not become pregnant while being treated with Valstar.
Men: Do not engage in sexual activity that could lead to pregnancy while being treated with Valstar.
●How should Valstar be given?
Valstar is administered using a special instrument, which is inserted into the patientｴs bladder. The patient will generally hold the drug for 2 hours before emptying their bladder. At the end of 2 hours, all patients should empty their bladder.
Be sure to drink plenty of fluids after treatment with Valstar.
●What are some possible side effects of Valstar?
(This is NOT a complete list of side effects reported with Valstar. Your health care provider can discuss with you a more complete list of side effects.)
Side effects with Valstar usually occur during or shortly after treatment and stop within 1 to 7 days after Valstar is removed from the bladder, including:
・Urinating too often
・Difficulty or pain during urination
・Urge to urinate immediately
・Bladder spasm
・Blood in the urine
・Bladder pain
・Inability to control urination
・Swelling of the bladder
・Waking up at night to urinate
・Burning sensation
Most side effects occurring outside the bladder are mild and disappear within 24 hours after treatment. These include stomach pain, nausea and urinary tract infections.
For more detailed information about Valstar, ask your health care provider.
Valstar's Approved Label★添付文書
●EMEA - Human Medcines
●List of Authorized Products (EPARs)★[A-Z 承認品目]
該当なし
Anthra Pharmaceuticals, Inc.は従業員33人のベンチャー。 Valstarは米国ではMedeva社を販売元とした。 又同社は高カルシウム血症治療薬Bonefosの米国内開発・販売権を独シェーリング社から獲得。
Anthra Pharmaceuticals, Inc.
KEYNUMBERS
Company Type: Private company
Nasdaq (SC): ANTH Proposed
Fiscal Year-End: June1998 Sales (mil.): $0.0
1-Yr. Sales Growth: (100.0%)
1998 Net Inc. (mil.): ($11.4)
1998 Employees: 33
1-Yr. Employee Growth: 10.0%
http://www.anthra.com
Anthra Pharmaceuticals has found a new pharmaceutical star in its Valstar bladder cancer treatment. The development-stage company acquires and develops late-stage drug candidates that treat bladder, ovarian, and prostate cancer, as well as complications from metastatic cancer. Anthra has licensed Valstar -- which was approved by the Food and Drug Administration in 1998 -- to Medeva for sale in the US. In addition, Anthra has acquired the US development and marketing rights to Bonefos, a treatment for hypercalcemia and lytic bone disease, from Schering AG. Anthra Pharmaceuticals has facilities in Europe and the US.
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■http://www.anthra.com
アンスラ社は制癌剤に特化した開発メーカー。 Valstarが最初の製品でFDA1998.9承認、1999.1に発売。 NASDAQ上場廃止3/15/1999
Medeva PLC is among the 13,000 companies for which Hoover's Online provides FREE information, including a corporate description, financial information, key officers, competitors and more；フーバー企業カプセル（13000社の無料企業情報）から
Date: 3 Dec 1998, Size 15.0K, http://www.hoovers.com/capsules/43055.html
Medeva PLC売上[1977]の66%が米国
●売上高等
Fiscal Year-End: December1997 Sales (mil.): $587.0［約734億円］
-Yr. Sales Growth: 3.3%
Net Inc. (mil.): $125.2
-Yr. Net Inc. Growth: 636.5%
Employees: 2,736
-Yr. Employee Growth: 13.8%
Annual Report on the Web
●会社概要
http://www.medeva.co.uk
Medeva develops and manufactures vaccines and prescription pharmaceuticals that treat central nervous system, respiratory, gastrointestinal, and dermatological conditions. The company's more than 30 products, which it makes and distributes primarily in Europe and the US, range from asthma and attention deficit disorder treatments to influenza vaccines and pain-management drugs. Medeva's US divisions concentrate on respiratory and antiobesity drugs and contract manufacturing of inhalation drug products. The company's development and vaccine research units develop new products and conduct clinical testing. Medeva is licensing from Targeted Genetics a therapy under development for cystic fibrosis.
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●
Corporate
Financial
New products
Products
Worldwide
RECENT CHANGES/ADDITIONS
th February, 1999
Job Opportunites at Medeva PLC15th February, 1999 E:mail form10th February, 1999 Medeva reports preliminery results for year ended 31st December 19985th February, 1999 Medeva disposes of non-core Swiss assets2nd February, 1999 Annual Report
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Press release, 10th February, 1999
MEDEVA PLC REPORTS PRELIMINARY RESULTS FOR THE YEAR ENDED 31st DECEMBER 1998
●HEPAGENE VACCINE SUBMISSION IN USA TODAY
HIGHLIGHTS
［略］
Hepagene: pan-European licence application for vaccine submitted;
US licence application for vaccine to be submitted to the Food and Drug Administration ("FDA") today.
New products Valstar and Asmabec Clickhaler launched; first revenues received in 1999.
Two new projects added to pipeline: tgAAV-CF, gene therapy for cystic fibrosis, and ConXn®, recombinant human relaxin, for scleroderma.
Commenced major infrastructure investment to expand vaccine facility at Speke.
Commenting on the results, Chairman John Baker said:
"With the exception of the CNS category, the rest of Medeva's business performed well in 1998 and we took advantage of our good cashflow to invest substantially in new products and facilities. In particular, we have considerably strengthened the potential of our new product development pipeline.
The anticipated decline of methylphenidate as our main revenue earner is taking place. The primary focus in 1999 is on the products in our pipeline which we believe have the potential to return Medeva to profits and earnings growth in subsequent years. Provided we continue to meet our milestones successfully, the pipeline has clear potential to generate significant long term value for shareholders."［略］
●EXTRACTS FROM THE ANNUAL REPORT AND ACCOUNTS FOR THE YEAR ENDED 31st DECEMBER 1998
OVERVIEW
Operating profit for 1998 has declined by £35m to £79m due to the anticipated competition to methylphenidate in the USA. The decline in methylphenidate sales was partially offset by a strong performance from a number of other products, notably Tussionex, Zaroxolyn and Fluvirin. Factors leading to the change in operating profit were as follows:
a £10.5m increase in profit contribution from non-CNS products excluding royalties to £53.2m, resulting from a 11% increase in sales to £221m and a contribution margin improvement to 24% (1997 : 21%); the majority of our profits now come from non-CNS products;
a 24% increase in royalty income to £8.4m;
a £41m decline in profit contribution from CNS products to £52m as a consequence of a 39% fall in sales to £76m and a decrease in contribution margin to 68% (1997 : 75%); and
a £5m increase in central and development costs to £35m mainly due to increased expenditure on the Phase III development of Hepagene.
Profit before tax for the year of £59m is after exceptional charges totalling £17m arising principally from the recycling of goodwill on the disposal of our International Medications Systems Limited ("IMS") business in the USA. For analysis of profit contribution see note 1.
●EXTRACTS FROM CHAIRMAN'S, CHIEF EXECUTIVE'S AND NEW PRODUCT DEVELOPMENT REPORTS
We continued to invest in and refine our infrastructure. We are supporting our vaccine business and our commitment to quality with a major investment programme to expand our vaccine development and production facility at Speke in the UK and an initial £21m has already been committed to the project. This will add significantly to Medeva's capabilities. We sold the US hospital products business, IMS, and, in April 1999, we will divest some of the assets of our Swiss manufacturing operation in order to keep our resources tightly focussed on our core businesses. We continue to market the IMS products in Europe where they complement our European hospital range.
Of increasing significance to the Group's future prosperity is the progress and strengthening of our new product development pipeline. We have met some significant milestones during 1998 and early 1999 and we are investing further in our development infrastructure. In summary, we:
filed a pan-European licence application for Hepagene Vaccine;
prepared a Biologics Licence Application for Hepagene Vaccine which is being submitted in the USA today;
reported encouraging results in our second Exploratory Development study with Hepagene Immunotherapy;
received a licence for Valstar in the USA as an Orphan Drug for the treatment of bladder cancer;
received a Marketing Authorisation in the UK for Asmabec Clickhaler for the treatment of asthma;
added a partnership with Targeted Genetics Corporation (":Targeted Genetics") to develop the gene therapy tgAAV-CF for cystic fibrosis;
added a partnership with Connetics Corporation ("Connetics") to develop ConXn® (recombinant human relaxin), as a treatment for scleroderma;
commenced Commercial Development of a codeine/chlorpheniramine-based cough treatment;
moved our hep B cores Platform Technology successfully into Exploratory Development; and moved our enteric-coated, delayed-release nicotine tartrate treatment for ulcerative colitis into Commercial Development.
●STRATEGIC DEVELOPMENT
●Medeva's opportunity in a changing pharmaceutical industry［略］
●Bringing new products to the market - Four stages of value creation［略］
●Medeva's attraction as a partner for research-based organisations
［略］
Two such partnerships were established in November 1998 and in January 1999: with Targeted Genetics, in the development of a gene therapy, tgAAV-CF, for the treatment of cystic fibrosis, and with Connetics, in the development of ConXn®, (recombinant human relaxin), as a treatment for scleroderma.
●Releasing unexploited value locked within large pharmaceutical companies［略］
●The criteria defining Medeva's targeted product opportunities［略］
●Medeva entering a new phase of its development［略］
●REGIONAL REVIEW
USA
In September 1998 the FDA granted a licence for the bladder cancer treatment, Valstar, and the product was launched by the US sales force, nationally, in January 1999. Valstar is one of Medeva's lead development projects, which was pursued in partnership with Anthra Pharmaceuticals Inc., this launch represents an important milestone for the Company.［略］
●EUROPE
The steroid version of our dry powder inhaler product, Asmabec Clickhaler, was granted a licence in the UK and the product was launched in November 1998. Asmabec contains beclomethasone dipropionate and is used for the prophylactic treatment of asthma. Early indications are that the product is being well received in the market and is also having a beneficial impact on sales of the salbutamol (albuterol) version of the product, Asmasal Clickhaler. This version, used for the relief of acute asthma attacks, was launched at the end of 1997.
［略］
At the beginning of February 1999 we announced that our Swiss manufacturing facility and certain related assets are to be sold to a company owned by members of the present local management team. Under the agreement, Medeva retains the rights to the royalty revenues from Asacol in the USA and Canada and to the intellectual property associated with the development of nicotine as a potential treatment for ulcerative colitis.
●EXTRACTS FROM THE OPERATING AND FINANCIAL REVIEW
COMPARABILITY WITH 1997
This review compares the 1998 Group financial performance with 1997 using like-for-like exchange rates. Since the majority of the Group's profits arise in the USA, the results as reported in sterling can be materially influenced by changes in the US dollar exchange rate. The average US dollar/sterling exchange rate for 1998 was $1.658, compared with $1.638 for 1997. Applying the 1997 historic exchange rates would increase 1998 reported sterling profit before tax by approximately £1.5m.
SALES
Overall CNS sales declined by £48m (39%) and non-CNS sales increased by £22m (11%).
Sales by Category (rounded - see note 11)
| |
1998 |
1997* |
Inc. (dec.)** |
| |
£m |
£m |
|
| |
|
|
|
| Methylphenidate |
68 |
112 |
(39%) |
| Ionamin |
8
|
12
|
(31%) |
CNS |
76
|
124
|
(39%) |
| |
|
: |
|
| Respiratory |
72 |
67 |
7% |
| Vaccines |
56 |
54 |
3% |
| Hospital Products |
38 |
32 |
18% |
| General |
56
|
46
|
20% |
| Total non-CNS |
221
|
199
|
11% |
| Royalties |
8 |
7 |
24% |
| Disposals and other*** |
16
|
22
|
|
| Group turnover |
321
|
352
|
(9%) |
* at 1998 average exchange rates
** % calculated to £0.1m and numbers rounded to nearest million
*** IMS US products disposed of on 8th October 1998 and Swiss products to be disposed of in April 1999
●Central Nervous System ("CNS")
The CNS category comprises two products, methylphenidate and Ionamin. Sales of methylphenidate, which is a generic drug prescribed primarily for the treatment of attention deficit hyperactivity disorder ("ADHD"), fell by 39% to £68m and accounted for 21% (1997 : 32%) of total Group sales. As anticipated, the decline resulted from the entry into the market of further generic competition leading to loss of market share, price erosion and a reduction in pipeline inventories.
Medeva's share of total prescriptions written (both generic and branded) fell to 55% (1997 : 72%), in a period in which there was no market growth. The fall in market share and a reduction in pipeline inventory resulted in a 30% fall in sales volume. This together with an average price decline of 13% led to the overall 39% decline in revenues. At least one more generic competitor is expected to enter the market in early 1999 and another is awaiting approval, both are likely to erode further Medeva's market share and increase the pressure on price. Accordingly, sales are expected to continue to decline.
Sales of Ionamin, our anti-obesity product, have shown some further decline in the second half of 1998, with market share of prescriptions falling to 6% for the year (H1 1998 : 7%). There continues to be no significant recovery in anti-obesity prescriptions following the concerns raised in mid-1997 about the health risks associated with the so-called "fen-phen diet".
●Respiratory
Sales of products in the respiratory category grew by 7% to £72m. Our main brand, Tussionex, the unique 12-hour anti-tussive, achieved sales of £29m, a 48% increase on 1997 levels. The increase was due to a 24% increase in prescriptions written, price increases and the reversal of low pipeline inventories at the end of December 1997. Delsym, the OTC extended-release paediatric cough product and our second largest respiratory product, achieved sales of £7m which was in line with 1997, in what was a weak "cough and cold" season. Semprex-D sales of £6m benefited from an almost empty product pipeline in December 1997 and price increases, which compensated for a decline in prescriptions written (12% down on 1997 levels) in the face of direct-to-consumer advertising from the main competitors in this market.
The performance of these three brands more than offset the continued generic erosion seen by our branded guaifenesin products, where sales of £6m showed a 48% decline over 1997.
Sales of generic albuterol MDI, marketed by Apothecon, at £6m (1997 : £4m), benefited from a full year in the growing US generic market albeit at depressed prices. This compensated for the decline in our lower margin US respiratory contract manufacturing business, where sales declined by £2m to £6m, mainly as one of our key customers moved production in-house during 1998.
The launch of the Asmabec Clickhaler in November 1998 enhanced our dry powder inhaler range; a full marketing campaign will support these products in 1999.
●Vaccines
Fluvirin sales increased again this year by 7% to £29m, as increased production was sold into the US market. We estimate that we have grown our share in the US market to 20% this year. Sales of our US diphtheria and tetanus products and Trivax were disappointing with sales declining £4m to £7m. US diphtheria and tetanus sales suffered from restricted availability from our US suppliers, ahead of the transfer of production to Speke which we expect to complete in mid-2000. Other vaccines sales increased 27% to £20m with a continued strong performance from our highly specialised contract manufacturing business based at Speke. Overall vaccine sales increased by 3%.
●Hospital Products
Sales of hospital products grew by 18% to £38m, with Zaroxolyn accounting for just under 50% of sales in this category. Zaroxolyn is a well established diuretic which is responding to active promotion in the USA for resistant oedema, a significant problem in congestive heart failure and severe renal disease. Prescription growth in 1998 was 12% (1997 : 9%) and this, together with price increases and the reversal of 1997 low pipeline inventories, increased sales by £6m to £18m.
Sales of other hospital products have grown by 2% with increased sales of diamorphine compensating for the reduced sales from IMS products in Europe due to a reduction in the number of products in this range. Prices in the US human market for isoflurane remain disappointing, although expansion in the export market continues.
●General Products
General product sales rose 20% to £56m and continue to represent a significant proportion of total sales (17% in 1998). This category contains many of our niche products and in 1998 includes both the gastrointestinal and dermatology ranges, which grew by 12% and 11% respectively. Our principal products in this category, Pediapred in the USA and Coracten in the UK, both achieved double-digit growth in sales, with 1998 sales of £6m being achieved by both products. In 1999 we will launch Coracten XL (extended-release) which will grow sales. This product category will also benefit from sales of Valstar in the USA in 1999.
●Royalties
The Group's royalty income grew by 24% to £8.4m (1997: £6.8m). Royalties arise principally on Asacol, which is licensed to Proctor & Gamble in the USA and Canada, and Pertactin (69kDa) which is licensed to SmithKline Beecham for inclusion in their acellular pertussis vaccine, Infanrix (trademark of SmithKline Beecham).
［略］
● SALES BY PRODUCT AND MAJOR THERAPEUTIC CATEGORY*
| |
1998 |
1997 |
% |
| |
£m |
£m |
Increase/ |
| Central Nervous System |
|
|
(decrease) |
| Methylphenidate |
68.0 |
112.1 |
|
| Ionamin |
8.1
|
11.8
|
|
| |
76.1
|
123.9
|
(39%) |
| Respiratory |
|
|
|
| Tussionex |
28.6 |
19.3 |
|
| Delsym |
6.9 |
7.3 |
|
| Guaifenesin based products |
5.8 |
11.1 |
|
| Semprex-D |
5.8 |
3.5 |
|
| Albuterol |
5.8 |
3.7 |
|
| Others |
19.0
|
22.1
|
|
| |
71.9
|
67.0
|
7% |
| Hospital Products |
|
|
|
| Zaroxolyn |
18.3 |
12.8 |
|
| Diamorphine |
4.9 |
4.3 |
|
| Others |
14.4
|
14.7
|
|
| |
37.6
|
31.8
|
18% |
| Vaccines |
|
|
|
| Fluvirin |
29.2 |
27.4 |
|
| DT and Trivax |
7.3 |
11.4 |
|
| Others |
19.5
|
15.4
|
|
| |
56.0
|
54.2
|
3% |
| |
8.4
|
6.8
|
24% |
| |
|
|
|
| General Products |
|
|
|
| Pediapred |
6.0 |
4.8 |
|
| Coracten |
5.7 |
4.9 |
|
| Dermatology |
7.0 |
6.3 |
|
| Others |
37.0
|
30.5
|
|
| |
55.7
|
46.5
|
20% |
| |
|
|
|
| Total net sales |
305.7 |
330.2 |
(7%) |
| Disposals and other adjustments ** |
15.7 |
21.3 |
|
| Currency adjustments |
-
|
3.9
|
|
| Total reported sales |
321.4
|
355.4
|
(10%) |
* Sales for both years are stated at 1998 average exchange rates.
** IMS US products disposed of on 8th October 1998 and Swiss products to be disposed of in April 1999
This page last updated Wednesday, 10th February, 1999
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