EP1596848A1 - Utilisation du compose 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-uree pour traiter des carcinomes pancreatiques, sarcomes des tissus mous, tumeurs testiculaires, lymphomes, thymomes, tumeurs de wilms, carcinomes renaux, melanomes, tumeurs pulmonaires, metastases intracerebrales, tumeurs dans la region de la tete et du cou et carcinome du sein - Google Patents

Utilisation du compose 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-uree pour traiter des carcinomes pancreatiques, sarcomes des tissus mous, tumeurs testiculaires, lymphomes, thymomes, tumeurs de wilms, carcinomes renaux, melanomes, tumeurs pulmonaires, metastases intracerebrales, tumeurs dans la region de la tete et du cou et carcinome du sein

Info

Publication number
EP1596848A1
EP1596848A1 EP04714277A EP04714277A EP1596848A1 EP 1596848 A1 EP1596848 A1 EP 1596848A1 EP 04714277 A EP04714277 A EP 04714277A EP 04714277 A EP04714277 A EP 04714277A EP 1596848 A1 EP1596848 A1 EP 1596848A1
Authority
EP
European Patent Office
Prior art keywords
tumors
treatment
hecnu
head
carcinomas
Prior art date
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Withdrawn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
EP04714277A
Other languages
German (de)
English (en)
Inventor
Gerhard Eisenbrand
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.)
Faustus Forschungs Cie Translational Cancer Research GmbH
Original Assignee
Faustus Forschungs Cie Translational Cancer Research GmbH
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.)
Filing date
Publication date
Application filed by Faustus Forschungs Cie Translational Cancer Research GmbH filed Critical Faustus Forschungs Cie Translational Cancer Research GmbH
Publication of EP1596848A1 publication Critical patent/EP1596848A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the invention relates to the use of 1- (2-chloroethyl) -1-nitroso-3- (2-hydroxyethyl) urea (hereinafter also "HECNU”) for the treatment of pancreatic carcinomas, soft tissue sarcomas, testicular tumors, lymphomas, thymomas, Wilms tumors, Kidney carcinomas, melanomas, lung tumors, intracerebral metastases, tumors in the head and neck area, and breast carcinomas.
  • HECNU 1- (2-chloroethyl) -1-nitroso-3- (2-hydroxyethyl) urea
  • BCNU bis- (2-chloroethyl) -1-nitroso-urea
  • HECNU Clinical phase II studies with HECNU for the treatment of malignant supratentorial gliomas have also been carried out, as described in J. Neuro-Oncology, 6, 211-219 (1988), P. Georges et al. described. HECNU also showed activity here. The favorable toxicity profile compared to other nitrosoureas is particularly emphasized.
  • phase II clinical studies with HECNU for the treatment of malignant, recurrent gliomas by intra-arterial and infra-ophthalmic infusion were carried out, as described in J. Neuro-Oncology, 8, 255-262 (1990), M. Poisson et al. described. This publication only describes the neuro-oncological area.
  • HECNU (1- (2-chloroethyl) -1-nitroso-3- (2-hydroxyethyl urea)
  • pancreatic carcinoma Treating soft tissue sarcoma, testicular tumor, lymphomas, thymomas, Wilms' tumors, kidney carcinomas, melanomas, lung tumors, intracerebral metastases, tumors in the head and neck area, and breast cancer.
  • the invention is therefore based on the object of treating pancreatic carcinomas, soft tissue sarcomas, testicular tumors, lymphomas, thymomas, Wilms tumors, melanomas, lung tumors, intracerebral metastases, tumors in the head and neck region, and breast carcinomas.
  • HECNU for use in the treatment of pancreatic carcinomas, soft tissue sarcomas, testicular tumors, lymphomas, thymons, Wilms tumors,
  • Renal carcinomas melanomas, lung tumors, intracerebral metastases, tumors in the head and neck area, and breast carcinomas are suitable.
  • HECNU is preferred for the treatment of pancreatic carcinomas, soft tissue sarcomas, lymphomas, thymomas, kidney carcinomas, melanomas, lung tumors, intracerebral metastases and tumors in the head and neck area.
  • HECNU is particularly preferred for the treatment of pancreatic carcinomas, soft tissue sarcomas, lymphomas, kidney carcinomas, melanomas, intracerebral metastases and tumors in the head and neck area.
  • HECNU is very particularly preferred for the treatment of pancreatic carcinomas, lymphomas, melanomas and tumors in the head and neck area. In vitro experiments, animal experiments and clinical studies have shown that HECNU is also very active in the treatment of these cancers.
  • HECNU has the following structural formula
  • HECNU shows - compared to BCNU - a significantly reduced bone marrow, lung and kidney toxicity. It is believed that this is due to the fact that when HECNU is used, no carbamoylation reactions can take place in the body, since no carbamoylating metabolite is formed in the body when it is broken down. In addition, HECNU does not inhibit glutathione reductase in the lungs. It is also a much weaker carcinogen compared to BCNU.
  • the compound can also be administered by simple injection.
  • HECNU shows only a low gastrointestinal toxicity and thus causes little nausea and little vomiting in patients and is better tolerated.
  • the invention also relates to the use of HECNU for the manufacture of a medicament for the treatment of pancreatic carcinomas, soft tissue sarcomas, testicular tumors, lymphomas, thymomas, Wilms Tumors, kidney carcinomas, melanomas, lung tumors, intracerebral metastases, tumors in the head and neck area, and breast carcinomas.
  • the invention further relates to a method for the therapeutic and / or prophylactic treatment of a mammal in need of treatment by administering HECNU for the treatment of pancreatic carcinomas, soft tissue sarcomas, testicular tumors, lymphomas, thymomas, Wilms tumors, kidney carcinomas, melanomas, lung tumors, intracerebral metastases, Tumors in the head and neck area, and breast cancer.
  • HECNU is particularly preferably administered intravenously, but also intramuscularly, intraperitoneally, subcutaneously or orally. External application is also possible. Administration by intravenous injection or intravenous infusion is preferred.
  • HECNU can be carried out in any suitable formulation, provided that the formation or maintenance of sufficient active substance levels is ensured. This can be achieved, for example, by oral or parenteral administration in suitable doses.
  • the pharmaceutical preparation of the active ingredient is advantageously in the form of unit doses which are tailored to the desired administration.
  • a unit dose can be, for example, a tablet, a dragee, a capsule, a suppository or a measured volume of a powder, a granulate, a solution, an emulsion or a suspension.
  • unit dose is understood to mean a physically determined unit which contains an individual amount of the active ingredient in combination with a pharmaceutical carrier and whose active ingredient content is a fraction or a multiple of one corresponds to a single therapeutic dose.
  • a single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half, a third or a quarter of a daily dose. If only a fraction, such as half or a quarter, of the unit dose is required for a single therapeutic administration, the unit dose is advantageously divisible, for example in the form of a tablet with a notch.
  • HECNU in a suitable medicament according to the invention can, if it is carried out in unit doses and for applications e.g. is intended for humans, with about 0.1 to 500 mg, preferably 10 to 200 mg and in particular 50 to 150 mg of active ingredient.
  • the active ingredient (s) are administered in a daily dose of 0.1 to 5, preferably 1 to 3 mg / kg body weight, optionally in the form of several, preferably 1 to 3, single doses to achieve the desired results.
  • a single dose contains the active ingredient (s) in amounts of 0.1 to 5, preferably 1 to 3 mg / kg body weight. Similar doses can be used in oral treatment.
  • HECNU The therapeutic use of HECNU according to the invention in a medicament can take place 1 to 4 times a day at fixed or varying times, for example in each case before meals and / or in the evening.
  • the determination of the required optimal dosage and type of application of HECNU can be done by any specialist based on his specialist knowledge.
  • the dose of HECNU administered to the patient is particularly preferably 60 to 200 mg / m 2 (based on the body surface of the patient), preferably approximately 80 to approximately 150 mg / m 2 , particularly preferably approximately 100 to approximately 120 mg / m 2 .
  • HECNU can take place in the form of medicaments, which as a rule comprise HECNU and non-toxic, pharmaceutically acceptable medicament carriers which are used as
  • Mixing or diluent for example in solid, semi-solid or liquid form or as a coating agent, for example in the form of a
  • Capsule, tablet cover, sachet or other container for the therapeutically active ingredient can be included in a carrier.
  • a carrier can e.g. as an intermediary for the
  • Sweetener as a flavor corrector, as a color or as
  • Tablets dragees e.g. come from gelatin, dispersible powders, granules, aqueous and oily suspensions, emulsions, solutions or syrups.
  • Tablets can contain inert diluents, for example calcium carbonate, calcium phosphate, sodium phosphate or lactose; Granulating and distributing agents, for example corn starch or alginates; Binders, e.g. starch, Gelatin or acacia; and lubricants, for example aluminum or magnesium stearate, talc or silicone oil. They can also be provided with a coating, which can also be designed in such a way that it causes a delayed dissolution and absorption of the pharmaceutical preparation in the gastrointestinal tract, so that, for example, better tolerance, protaction or retardation is achieved.
  • Gelatin capsules can be mixed with a solid, for example calcium carbonate or kaolin, or an oily, for example olive, peanut or paraffin oil,
  • Aqueous suspensions can include suspending agents, e.g.
  • Dispersing and wetting agents e.g. Polyoxyethylene stearate, heptadecaethyleneoxycatanol, polyoxyethylene sorbitol monooleate or lecithin; Preservatives, e.g. Methyl or propyl hydroxybenzoates; Flavoring agents; Sweeteners, e.g. Sucrose, lactose, sodium cyclamate, dextrose, invert sugar syrup.
  • Oily suspensions can e.g. Peanut, olive, sesame, coconut or paraffin oil and thickeners such as e.g. Beeswax, hard paraffin or cetyl alcohol; also sweeteners, flavoring agents and antioxidants.
  • Water-dispersible powders and granules can be used in the use of HECNU in accordance with the invention in a mixture with dispersing, wetting and suspending agents, e.g. the above, as well as with sweeteners, flavorings and colorants.
  • Emulsions can be, for example, olive, peanut or paraffin oil in addition to emulsifiers, such as, for example, acacia, tragacanth, phosphatides, sorbitan monooleate, polyoxyethylene sorbitan monooleate, and sweeteners and Contain flavoring.
  • emulsifiers such as, for example, acacia, tragacanth, phosphatides, sorbitan monooleate, polyoxyethylene sorbitan monooleate, and sweeteners and Contain flavoring.
  • Aqueous solutions can contain preservatives, e.g. Methyl or propyl hydroxybenzoates; Thickener; Flavoring agents;
  • Sweeteners e.g. Contain sucrose, lactose, sodium cyclamate, dextrose, invert sugar syrup, as well as flavorings and colorings.
  • Sterile injectable, aqueous solutions, isotonic saline solutions or other solutions are used for parenteral use of the medicinal substances.
  • pancreatic cancer pancreatic cancer
  • HECNU human tumor xenograft models in the nude mouse
  • human xenograft tumor models in the nude mouse showed good to very good inhibitory effects on tumor growth in a representative spectrum of tumors.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation du composé 1-(2-chloroéthyl)-1-nitroso-3-(2-hydroxyéthyl)-urée (ou </= HECHNU >/= ) pour traiter des carcinomes pancréatiques, sarcomes des tissus mous, tumeurs testiculaires, lymphomes, thymomes, tumeurs de Wilms, carcinomes rénaux, mélanomes, tumeurs pulmonaires, métastases intracérébrales, tumeurs dans la zone de la tête et du cou, ainsi que des carcinomes mammaires.
EP04714277A 2003-02-25 2004-02-25 Utilisation du compose 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-uree pour traiter des carcinomes pancreatiques, sarcomes des tissus mous, tumeurs testiculaires, lymphomes, thymomes, tumeurs de wilms, carcinomes renaux, melanomes, tumeurs pulmonaires, metastases intracerebrales, tumeurs dans la region de la tete et du cou et carcinome du sein Withdrawn EP1596848A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10307928A DE10307928A1 (de) 2003-02-25 2003-02-25 Verwendung von 1-(2-Chlorethyl)-1-nitroso-3-(2-hydroxyethyl)-urea zur Behandlung von Pankreaskarzinomen, Weichteilsarkomen, Hodentumoren, Lymphomen, Thymomen, Wilms Tumoren, Nierenkarzinomen, Melanomen, Lungentumoren, intracerebralen Metastasen, Tumoren im Kopf- und Halsbereich, und Mamma-Karzinomen
DE10307928 2003-02-25
PCT/EP2004/001875 WO2004075887A1 (fr) 2003-02-25 2004-02-25 Utilisation du compose 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-uree pour traiter des carcinomes pancreatiques, sarcomes des tissus mous, tumeurs testiculaires, lymphomes, thymomes, tumeurs de wilms, carcinomes renaux, melanomes, tumeurs pulmonaires, metastases intracerebrales, tumeurs dans la zone de la tete et du co

Publications (1)

Publication Number Publication Date
EP1596848A1 true EP1596848A1 (fr) 2005-11-23

Family

ID=32863868

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04714277A Withdrawn EP1596848A1 (fr) 2003-02-25 2004-02-25 Utilisation du compose 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-uree pour traiter des carcinomes pancreatiques, sarcomes des tissus mous, tumeurs testiculaires, lymphomes, thymomes, tumeurs de wilms, carcinomes renaux, melanomes, tumeurs pulmonaires, metastases intracerebrales, tumeurs dans la region de la tete et du cou et carcinome du sein

Country Status (6)

Country Link
US (1) US20060025484A1 (fr)
EP (1) EP1596848A1 (fr)
JP (1) JP2006518722A (fr)
CA (1) CA2555746A1 (fr)
DE (1) DE10307928A1 (fr)
WO (1) WO2004075887A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8053430B2 (en) 2008-10-06 2011-11-08 Haraldsson Boerje Treatment of renal cell carcinoma
JP2013523726A (ja) 2010-04-01 2013-06-17 オンコレナ エービー 腎細胞癌の改良された治療

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5001158A (en) * 1984-04-11 1991-03-19 Centre National De La Recherche Scientifique Nitrosoureas compounds preparation thereof and utilization thereof in anticancerous
US5525606A (en) * 1994-08-01 1996-06-11 The United States Of America As Represented By The Department Of Health And Human Services Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines
WO1999001118A2 (fr) * 1997-07-01 1999-01-14 Atherogenics, Inc. Amelioration au moyen d'antioxydants de la therapie destinee aux etats d'hyperproliferation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
PREISS, DORNOFF, HAGMANN, SCHMIEDER: "ONKOLOGIE", 2002, ZUCKERSCHWERDT VERLAG GMBH *
See also references of WO2004075887A1 *

Also Published As

Publication number Publication date
DE10307928A1 (de) 2004-09-16
WO2004075887A1 (fr) 2004-09-10
JP2006518722A (ja) 2006-08-17
US20060025484A1 (en) 2006-02-02
CA2555746A1 (fr) 2004-09-10

Similar Documents

Publication Publication Date Title
DE10103565B4 (de) Zusammensetzungen, enthaltend einen Ruthenium(III)-komplex und einen Heterocyclus
DE4127737A1 (de) Arzneimittel zur behandlung von abstossungsreaktionen bei organverpflanzungen
EP1984005B1 (fr) Utilisation de complexes de gallium (iii) pour le traitement de mélanomes
DE2923334C2 (de) Verwendung von Cyclopentadienylmetall-Acido-Komplexen bei der Krebsbekämpfung und diese Komplexe enthaltende Arzneipräparate
DE4024885A1 (de) Verwendung von 2-phenyl-1,2-benzisoselenazol-3(2h)-on
EP1596848A1 (fr) Utilisation du compose 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)-uree pour traiter des carcinomes pancreatiques, sarcomes des tissus mous, tumeurs testiculaires, lymphomes, thymomes, tumeurs de wilms, carcinomes renaux, melanomes, tumeurs pulmonaires, metastases intracerebrales, tumeurs dans la region de la tete et du cou et carcinome du sein
AT501819B1 (de) Verwendung von gallium(iii)-komplexen zur behandlung von tumorerkrankungen der leber
DE10113185A1 (de) Zusammensetzung, enthaltend einen Gallium(III)-Komplex und einen therapeutisch wirksamen Platin-Komplex
WO1997036595A2 (fr) Preparations medicamenteuses contenant des complexes de ruthenium (iii) a action antitumorale
DE10114222C1 (de) Tumorhemmende Siliciumverbindungen, Verfahren zu ihrer Herstellung und deren Verwendung
AT505367A1 (de) Tumorhemmende ruthenium und osmium- thiosemicarbazonatokomplexe
DE3134709A1 (de) Antineoplastisch wirkende titanverbindung und diese enthaltende arzneimittel
DE10116527C2 (de) Tumorhemmende Galliumverbindungen, deren Verwendung als Arzneimittel sowie ein Arzneimittel, diese enthaltend
DE10138561B4 (de) Tumorhemmende Cerverbindungen sowie deren Verwendung
DE10138538C2 (de) Tumorhemmende Lanthanverbindungen
DE10114106C1 (de) Tumorhemmende Siliciumverbindungen, Verfahren zu ihrer Herstellung und deren Verwendung als Arzneimittel
AT501262B1 (de) Verwendung von gallium(iii)-komplexen zur behandlung von tumoren des urothelialtraktes
DE68907971T2 (de) Verwendung von Spergualin-Derivaten gegen Nebenwirkungen radiologischen oder medikamentösen Ursprungs.
DE2449591A1 (de) Neues kombinationsarzneimittel
DE2737604A1 (de) Neues kombinationsarzneimittel
DE3048109A1 (de) Antineoplastisch wirkende arzneimittel
AT503592A1 (de) Tumorhemmende galliumverbindungen
DE3037665A1 (de) Cytostatisch wirkende arzneimittel

Legal Events

Date Code Title Description
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

17P Request for examination filed

Effective date: 20050920

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK

DAX Request for extension of the european patent (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RTI1 Title (correction)

Free format text: USE OF 1-(2-CHLOROETHYL)-1-NITROSO-3-(2-HYDROXYETHYL)-UREA FOR THE TREATMENT OF PANCREATIC CANCER, LYMPHOMA, HEAD AND NECK TUMORS

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

18D Application deemed to be withdrawn

Effective date: 20070704

R18D Application deemed to be withdrawn (corrected)

Effective date: 20070703