EP0572563A1 - Behandlung von ösophaguskrebs - Google Patents

Behandlung von ösophaguskrebs

Info

Publication number: EP0572563A1
Authority: EP; European Patent Office
Prior art keywords: hydroxy; course; compound; topotecan; therapy
Prior art date: 1991-02-21
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

EP92908199A

Other languages

English (en)

French (fr)

Other versions

EP0572563A4 (en

Inventor

Randall Keith Johnson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

SmithKline Beecham Corp

Original Assignee

SmithKline Beecham Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-02-21

Filing date

1992-02-07

Publication date

1993-12-08

1992-02-07 Application filed by SmithKline Beecham Corp filed Critical SmithKline Beecham Corp

1993-12-08 Publication of EP0572563A1 publication Critical patent/EP0572563A1/de

1993-12-29 Publication of EP0572563A4 publication Critical patent/EP0572563A4/en

Status Withdrawn legal-status Critical Current

Links

208000000461 Esophageal Neoplasms Diseases 0.000 title claims abstract description 17
206010030155 Oesophageal carcinoma Diseases 0.000 title claims abstract description 16
201000004101 esophageal cancer Diseases 0.000 title claims abstract description 16
238000011282 treatment Methods 0.000 title claims abstract description 12
150000001875 compounds Chemical class 0.000 claims abstract description 31
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
238000002560 therapeutic procedure Methods 0.000 claims description 36
UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 35
229960000303 topotecan Drugs 0.000 claims description 35
238000000034 method Methods 0.000 claims description 24
-1 cyclohexylaminomethyl Chemical group 0.000 claims description 17
238000001990 intravenous administration Methods 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 10
238000001802 infusion Methods 0.000 claims description 9
239000012453 solvate Substances 0.000 claims description 7
150000004677 hydrates Chemical class 0.000 claims description 6
239000000203 mixture Substances 0.000 claims description 6
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 4
238000007911 parenteral administration Methods 0.000 claims description 4
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000006317 cyclopropyl amino group Chemical group 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 abstract description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
206010028980 Neoplasm Diseases 0.000 description 8
108020004414 DNA Proteins 0.000 description 7
102000003915 DNA Topoisomerases Human genes 0.000 description 6
108090000323 DNA Topoisomerases Proteins 0.000 description 6
238000002360 preparation method Methods 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
239000000243 solution Substances 0.000 description 4
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229940127093 camptothecin Drugs 0.000 description 3
239000000039 congener Substances 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 3
210000003527 eukaryotic cell Anatomy 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
230000000977 initiatory effect Effects 0.000 description 3
238000011084 recovery Methods 0.000 description 3
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
101710183280 Topoisomerase Proteins 0.000 description 2
239000002585 base Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
238000005057 refrigeration Methods 0.000 description 2
239000008354 sodium chloride injection Substances 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
238000013518 transcription Methods 0.000 description 2
230000035897 transcription Effects 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
208000017897 Carcinoma of esophagus Diseases 0.000 description 1
108010077544 Chromatin Proteins 0.000 description 1
102000053602 DNA Human genes 0.000 description 1
230000004543 DNA replication Effects 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
159000000021 acetate salts Chemical class 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
150000003797 alkaloid derivatives Chemical class 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
239000008366 buffered solution Substances 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
230000003915 cell function Effects 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000033077 cellular process Effects 0.000 description 1
230000000973 chemotherapeutic effect Effects 0.000 description 1
210000003483 chromatin Anatomy 0.000 description 1
230000002759 chromosomal effect Effects 0.000 description 1
238000012398 clinical drug development Methods 0.000 description 1
230000001461 cytolytic effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000008355 dextrose injection Substances 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
231100000371 dose-limiting toxicity Toxicity 0.000 description 1
229940079593 drug Drugs 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
238000009472 formulation Methods 0.000 description 1
230000012010 growth Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
210000001165 lymph node Anatomy 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
238000000053 physical method Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000010076 replication Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000005783 single-strand break Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008227 sterile water for injection Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000012360 testing method Methods 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Definitions

This invention relates to a method of treating esophageal cancer in a human afflicted therewith which comprises administering to such human an effective amount of a compound of the water soluble camptothecin analog class, such as topotecan.
the structure of the DNA helix within eukaryotic cells imposes certain topological problems that the cellular apparatus must solve in order to use its genetic material as a template.
the separation of the DNA strands is fundamental to cellular processes such as DNA replication and transcription. Since eukaryotic DNA is organized into chromatin by chromosomal proteins, the ends are constrained and the strands cannot unwind without the aid of enzymes that alter topology. It has long been recognized that the advancement of the transcription or replication complex along the DNA helix would be facilitated by a swivel point which would relieve the torsional strain generated during these processes.
Topoisomerases are enzymes that are capable of altering DNA topology in eukaryotic cells. They are critical for important cellular functions and cell proliferation. There are two classes of topoisomerases in eukaryotic cells, type I and type II.
Topoisomerase I is a monomeric enzyme of approximately 100,000 molecular weight. The enzyme binds to DNA and introduces a transient single-strand break, unwinds the double helix (or allows it to unwind) , and subsequently reseals the break before dissociating from the DNA strand. Camptothecin, a water-insoluble alkaloid produced by trees indigenous to China and India, and a few other congeners thereof, are the only class of compounds known to inhibit topoisomerase I.
Camptothecin and other topoisomerase I inhibiting congeners have not proven to be attractive for clinical drug development as cytolytic agents because of lack of clinical efficacy, unacceptable dose- limiting toxicity, unpredictable toxicity, poor aqueous solubility, and/or unacceptable shelf life stability.
topoisomerase I inhibiting agents which avoid the aforementioned undesirable features of camptothecin and related topoisomerase I inhibiting congeners.
Topotecan or any compound of the water soluble camptothecin analog class, is a specific -inhibitor of DNA topoisomerase I which fulfills such need.
This invention relates to a method of treating esophageal cancer in a human afflicted therewith which comprises administering to such human an effective amount of a compound of the water soluble camptothecin analog class.
This invention also relates to a method of treating esophageal cancer in a human afflicted therewith which comprises administering to such human an effective amount of topotecan.
a compound of the water soluble camptothecin analog class is meant any compound claimed in U.S. Patent Number 5,004,758, the entire disclosure of which is hereby incorporated by reference.
the preparation of any compound of the water soluble camptothecin analog class (including pharmaceutically acceptable salts, hydrates and solvates thereof) as well as the preparation of oral and parenteral pharmaceutical compositions comprising a compound of the water soluble camptothecin analog class and an inert, pharmaceutically acceptable carrier or diluent, is extensively described in U.S. Patent Number 5,004,758. The same extensive description is found in European Patent Application Number 88311366.4, published on June 21, 1989 as
Preferred compounds of the water soluble camptothecin analog class include those compounds of the formula:
X is hydroxy and R is trimethylammoniummethyl; b) X is hydroxy and R is N- methylpiperazinylmethyl/ c) X is hydroxy and R is N-methylanilinomethyl; d) X is hydroxy and R is cyclohexylaminomethyl; e) X is hydroxy and R is N,N- dimethylaminoethyloxymethy1/ f) X is hydroxy and R is cyclopropylaminomethy1; g) X is hydroxy and R is morpholinomethyl; h) X is hydroxy and R is aminomethyl; and i) X is hydroxy and R is cyanomethyl; and j) X is hydroxy and R is dimethylaminomethyl or any pharmaceutically acceptable salts, hydrates and solvates thereof.
Topotecan is the most preferred compound of the water soluble camptothecin analog class.
Topotecan is water-soluble by virtue of the presence of the basic side-chain at position 9 which forms salts with acids.
Preferred salt forms of topotecan include the hydrochloride salt, acetate salt and ethanesulfonic acid salt.
a alkali metal salt form of the carboxylate formed on alkaline hydrolysis of the E-ring lactone of topotecan would also yield a soluble salt, such as the sodium salt.
topotecan including pharmaceutically acceptable salts, hydrates and solvates thereof
oral and parenteral pharmaceutical compositions comprising topotecan and an inert, pharmaceutically acceptable carrier or diluent
European Patent Application Number 88311366.4 published on June 21, 1989 as Publication Number EP 0 321 122.
This invention relates to a method of treating esophageal cancer in a human afflicted therewith which
One preferred aspect of this invention relates to a method of treating esophageal cancer in a human afflicted therewith which comprises administering to such human an effective amount of topotecan.
esophageal cancer cancer of the esophagus .
treating esophageal cancer is meant the inhibition of the growth of esophageal cancer cells.
treatment also leads to the regression of tumor growth, i.e., the decrease in size of a measurable tumor.
such treatment leads to the complete regression of the tumor.
parenteral is meant intravenous, subcutaneous and intramuscular administration.
effective amount of a compound of the water soluble camptothecin analog class and “effective amount of topotecan” as used herein is meant a course of therapy which will result in treating esophageal cancer. It will be appreciated that the actual preferred course of therapy will vary according to, inter alia, the mode of administration, the particular formulation of a compound of the water soluble camptothecin analog class (such as topotecan) being utilized, the mode of administration and the particular host being treated.
the course of therapy generally employed is from about 0.5 to about 2 5 25.0 mg/m of body surface area per day for about one to about five consecutive days. More preferably, the course of therapy employed is from about 1.0 to about
2 10 therapy employed is from about 1.5 to about 2 mg/m of body surface area per day for about five consecutive days.
the course of therapy is repeated at least once at about a seven day to about a twenty-eight day interval (from the date of initiation of therapy)
the parenteral administration will be any suitable parenteral administration.
the parenteral administration will be any suitable parenteral administration.
the topotecan will be administered by a 30 minute intravenous infusion.
25 preferred course of parenteral therapy to be employed with topotecan for a previously non-treated or lightly pretreated patient is an initial course of therapy of
course of therapy of 1.5 mg of topotecan/m of body surface area per day is administered by short intravenous infusion for five consecutive days, such course of therapy to be repeated based on tumor response.
the course of therapy generally employed is from about 1.0 to about 2 50.0 mg/m of body surface area per day for about one to five consecutive days. More preferably, the course of
2 therapy employed is from about 1.5 to about 5.0 mg/m of body surface area per day for about five consecutive days.
the course of therapy is repeated at least once at about a seven day to about a twenty-eight day interval (from the date of initiation of therapy) depending upon the initial dosing schedule and the patient's recovery of normal tissues. Most preferably, the course of therapy continues to be repeated based on tumor response.
Topotecan is currently undergoing Phase I clinical investigation.
the following pharmaceutical information is being supplied to the clinicians:
Topotecan diluted in saline (10 ug/ml or 500 ug/ml) or dextrose (6.7 ug/ml or 330 ug/ml) is stable in a hang-bag for 24 hours with at least 95% recovery.
Treatment dose The treatment dose is to be diluted in a final volume of 150 ml of Sodium Chloride Injection, USP (without preservatives) and administered over a 30 minute period.
the treatment dose is to be kept under refrigeration and protected from light and it is to be used within 24 hours.
One human patient with metastatic esophageal cancer who was refractory to at least one previous chemotherapeutic regimen with a compound or compounds other than a water soluble camptothecin analog, received a course of therapy comprising intravenous

Landscapes

Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

EP19920908199 1991-02-21 1992-02-07 Treatment of esophageal cancer Withdrawn EP0572563A4 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US65893691A	1991-02-21	1991-02-21
US658936		1991-02-21

Publications (2)

Publication Number	Publication Date
EP0572563A1 true EP0572563A1 (de)	1993-12-08
EP0572563A4 EP0572563A4 (en)	1993-12-29

Family

ID=24643326

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EP19920908199 Withdrawn EP0572563A4 (en)	1991-02-21	1992-02-07	Treatment of esophageal cancer

Country Status (8)

Country	Link
EP (1)	EP0572563A4 (de)
JP (1)	JPH06505487A (de)
KR (1)	KR930702985A (de)
AU (1)	AU664172B2 (de)
CA (1)	CA2104449A1 (de)
MX (1)	MX9200725A (de)
PT (1)	PT100154A (de)
WO (1)	WO1992014470A1 (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6395541B1 (en)	1996-05-23	2002-05-28	The Rockefeller University	Methods for the identification of compounds capable of inhibiting HIV-1 viral replication employing murine cell lines expressing human topoisomerase I
WO2001066144A2 (en) *	2000-03-08	2001-09-13	Rhode Island Hospital, A Lifespan Partner	Antineoplastic combination comprising an inhibitor of angiogenesis and an inhibitor of dna topoisomerase i enzyme activity
CA2404431C (en)	2000-03-27	2011-06-07	Thomas Jefferson University	Guanylyl cyclase c in the detection of stomach and esophageal cancers
US8053183B2 (en) *	2005-07-27	2011-11-08	Oncotherapy Science, Inc.	Method of diagnosing esophageal cancer
ES2371171B1 (es) *	2010-06-08	2012-11-16	Consejo Superior De Investigaciones Científicas (Csic)	Derivados de camptotecina como agentes antitumorales.
CN102659800B (zh) *	2012-05-11	2014-09-03	中国药科大学	一类低氧激活抗肿瘤化合物及其用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0321122A2 (de) *	1987-12-01	1989-06-21	Smithkline Beecham Corporation	Wasserlösliche Camptothecin-Analoge

1992
- 1992-02-07 EP EP19920908199 patent/EP0572563A4/en not_active Withdrawn
- 1992-02-07 AU AU15406/92A patent/AU664172B2/en not_active Ceased
- 1992-02-07 JP JP4507807A patent/JPH06505487A/ja active Pending
- 1992-02-07 CA CA002104449A patent/CA2104449A1/en not_active Abandoned
- 1992-02-07 WO PCT/US1992/001029 patent/WO1992014470A1/en not_active Application Discontinuation
- 1992-02-07 KR KR1019930702492A patent/KR930702985A/ko not_active Application Discontinuation
- 1992-02-21 MX MX9200725A patent/MX9200725A/es unknown
- 1992-02-21 PT PT100154A patent/PT100154A/pt not_active Application Discontinuation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0321122A2 (de) *	1987-12-01	1989-06-21	Smithkline Beecham Corporation	Wasserlösliche Camptothecin-Analoge

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CANCER CHEMOTHER REP. vol. 56, no. 1 , 1972 pages 95 - 101 C.G. MOERTEL ET AL 'Phase II study of camptothecin (NSC 100880) in the treatment of advanced gastrointestinal cancer.' *
PROC. AM. ASSOC. CANCER RES. ANNU. MEET. vol. 31 , 1990 page 436 M.R. MATTERN ET AL 'Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor SKF 104864.' *
PROC. ANNU. MEET. AM. SOC. CLIN. ONCOL. vol. 10 , 1991 page 117 Y. OHE ET AL 'Pharmacokinetics with a 5-day continuous infusion of a camptothecin derivative, CPT-11.' *
See also references of WO9214470A1 *

Also Published As

Publication number	Publication date
CA2104449A1 (en)	1992-08-22
PT100154A (pt)	1993-05-31
WO1992014470A1 (en)	1992-09-03
JPH06505487A (ja)	1994-06-23
KR930702985A (ko)	1993-11-29
EP0572563A4 (en)	1993-12-29
MX9200725A (es)	1992-09-01
AU664172B2 (en)	1995-11-09
AU1540692A (en)	1992-09-15

Publication	Publication Date	Title
EP0612248B1 (de)	2003-08-20	Cisplatin und Topotecan enthaltende Zusammensetzung als antitumor.
US5674872A (en)	1997-10-07	Treatment of ovarian cancer
AU2394392A (en)	1993-07-19	Treatment of colorectal cancer
AU664172B2 (en)	1995-11-09	Treatment of esophageal cancer
US5756512A (en)	1998-05-26	Treatment of non-small cell lung carcinoma
EP1707568B1 (de)	2010-08-04	Pharmazeutische Zusammensetzung zur Verwendung in der Behandlung von Eierstockkrebs

Legal Events

Date	Code	Title	Description
1993-10-22	PUAI	Public reference made under article 153(3) epc to a published international application that has entered the european phase	Free format text: ORIGINAL CODE: 0009012
1993-12-08	17P	Request for examination filed	Effective date: 19930823
1993-12-08	AK	Designated contracting states	Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU MC NL SE
1993-12-29	A4	Supplementary search report drawn up and despatched	Effective date: 19931111
1993-12-29	AK	Designated contracting states	Kind code of ref document: A4 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU MC NL SE
1998-01-28	17Q	First examination report despatched	Effective date: 19971211
1998-08-28	STAA	Information on the status of an ep patent application or granted ep patent	Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN
1998-10-14	18D	Application deemed to be withdrawn	Effective date: 19980422
2005-09-16	REG	Reference to a national code	Ref country code: HK Ref legal event code: WD Ref document number: 1012266 Country of ref document: HK