EP1091744A1 - 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (et180ch3) pour traiter les cancers du sein humains - Google Patents

1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (et180ch3) pour traiter les cancers du sein humains

Info

Publication number
EP1091744A1
EP1091744A1 EP99932780A EP99932780A EP1091744A1 EP 1091744 A1 EP1091744 A1 EP 1091744A1 EP 99932780 A EP99932780 A EP 99932780A EP 99932780 A EP99932780 A EP 99932780A EP 1091744 A1 EP1091744 A1 EP 1091744A1
Authority
EP
European Patent Office
Prior art keywords
treatment
breast cancer
et180ch3
cancer
breast
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Withdrawn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
EP99932780A
Other languages
German (de)
English (en)
Inventor
Apollonia Nagler
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.)
MedMark Pharma GmbH
Original Assignee
MedMark Pharma 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 MedMark Pharma GmbH filed Critical MedMark Pharma GmbH
Publication of EP1091744A1 publication Critical patent/EP1091744A1/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Withdrawn legal-status Critical Current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
    • A61K31/66—Phosphorus compounds

Definitions

  • the invention relates to ET1 8OCH3 (1-octadecyl-2-methyl-sn-glycero-3-phosphocholine, also known as edelfosin, INN) for the treatment of human breast cancer.
  • the treatment of breast cancer is a serious and still unsolved problem in an aging population and especially in countries where the population has unhindered access to medicines and clinics.
  • the therapeutic approaches for breast cancer include surgery, radiation and systemic drug treatment (chemotherapy), which is the preferred treatment for this type of cancer in order to eliminate the risk of recurrence and metastasis as far as possible.
  • chemotherapy systemic drug treatment
  • occult metastases are already present in every second case when the diagnosis is made.
  • postoperative radiation is often not sufficient and systemic therapy must follow, because depending on the location of the irradiated area and the amount of the radiation dose used, there is an increased risk of developing carcinoma of the esophagus years later (Ahsan 1 998 ).
  • Chemotherapy which has an undisputed place in the treatment of breast cancer, has the major disadvantage that it can only be used for a limited time.
  • the undesirable drug effects (UAW) caused by the effective therapeutic regimens are known and feared (Petru et al. 1 987).
  • the newest group of cytostatics, the so-called taxanes have particularly severe ADRs, which even include the exitus letalis as drug-induced (specialist information from Taxol and Taxotere).
  • adjuvant chemotherapy which can be used for a limited time, cannot effectively prevent metastatic involvement of the lungs, liver, pleura or bone compared to placebo therapy for breast cancer with lymph node involvement (Goldhirsch et al. 1 994).
  • hormone preparations in particular are used in the treatment, with the aim of influencing tumor growth by administering or withdrawing hormones.
  • hormone treatments have less severe ADR than the classic cytostatics, so that long-term use of hormone preparations is even possible.
  • hormone treatment also has serious disadvantages.
  • the application is limited to tumors with a positive hormone receptor status, and resistance formation often occurs during therapy due to a change in the hormone receptor status.
  • hormone preparations also have UAW.
  • a well-known example is tamoxifen, of which no less than 40 side effects are known (Bulbrook 1 996).
  • many hormone preparations themselves have a carcinogenic effect.
  • tamoxifen blocks e.g. the estrogen receptors on the breast, but has estrogen-like effects in other organs. Women treated in this way are more likely to develop endometrial cancer, but also gastrointestinal tumors and thromboembolism. If hormones are administered as part of a normal, i.e. non-therapeutic, substitution over a period of 10 years, the risk of developing breast cancer increases by 30% (Bulbrook 1 996). Regardless of the purpose of the cancer treatment, it should not be overlooked the fact that the increased intake of hormones can also cause other side effects, such as infertility in humans and animals.
  • ET1 8OCH3 as an active ingredient for a medicament for the treatment of breast cancer.
  • ET1 8OCH3 is a phospholipid analogue and because of its similarity to the phospholipids of the cell membranes has a high affinity for the membranes themselves. The uptake in the cells is therefore independent of the receptor (Snyder 1 991). In contrast to hormone preparations, the receptor status is irrelevant. Another great advantage of ET1 8OCH3 compared to other substances used for systemic chemotherapy is that the molecule only acts selectively on tumor cells and not on normal, healthy body cells or organs (Hickmann 1,992). In healthy, non-tumorous cells, ET1 80CH3 is broken down (Magistrelli et al. 1 994). A compelling and logical consequence of this selectivity is that ET180CH3 is neither mutagenic (King et al.
  • a drug that is given over a longer period of time should therefore also induce re-induction of apoptosis in the tumor cells.
  • the drug can be administered over a practically unlimited period of time, so that the tumor cells are permanently influenced in their division behavior.
  • the longest duration of therapy for a patient with breast cancer was 281 1 days. The patient did not suffer from any significant adverse drug effects. There were no recurrences or metastases (see Table 1).
  • ET1 80CH3 has been shown to inhibit the formation of new vessels in tumor tissue (Candal et al., 1 994). ET1 80CH3 is also antimetastatic, as demonstrated by Berdel et al., 1 982, and Storme et al., 1 985, on a highly invasive carcinoma model.
  • ET1 80CH3 The pharmacodynamic effects of ET1 80CH3, especially on the breast cancer model, have been tested on animals both in vitro and in vivo.
  • Using the human MDA-MB 231 breast carcinoma cell line, it was demonstrated in the nude mouse model that the administration of ET1 80CH3 leads to an inhibition of tumor growth or a significant mitotic index ( number of dividing cells) compared to controls (Hardman et al. 1 997).
  • Treating cells with ET1 80CH3 will increase the absorption of estradiol inhibited depending on dose. This effect can be measured before the growth-inhibiting effect of ET1 80CH3 occurs (Kosano et al. 1 990).
  • ET1 80CH3 has the following advantages over the substances used in the prior art:
  • the most important prognostic factor is the number of affected axillary lymph nodes (LK) when diagnosed. From stage N1 /> 3 LK + (i.e.> 3 histologically examined lymph nodes are tumorous) the risk of a subsequent metastasis increases up to 90%.
  • the so-called "high-risk" cases which have particularly unfavorable prognostic factors, are therefore particularly meaningful when evaluating the effectiveness of a therapy. See cases No. 2, No. 6, No. 7, No. 8, No. 1 1 of Table 1.
  • a drug should ideally be combinable with commonly used drugs; there should be no multi-drug resistance reactions, nor should it affect the effectiveness of chemotherapy if it is used after the "new" therapy. See cases No. 1 2, No. 14, No. 1 5, No. 1 6, No. 1 7 of Table 1.
  • the carrier medium is preferably a water-based drink, in particular milk.
  • ET1 8OCH3 can easily be administered orally.
  • suitable carrier materials can include soups (in particular alloyed soups), beer, egg liqueur and other conventional beverages. Milk-based carriers such as milk substitute, yogurt, kefir and the like are also suitable.
  • the carrier medium-active ingredient mixture is taken throughout the day, e.g. drunk. The application is therefore oral. Treatment is entirely outpatient, unless the clinical picture makes inpatient admission inevitable.
  • the rating “yes” means that a symptom is caused by the drug.
  • the rating “questionable” means that the cause of the complaint is unclear.
  • the UAW caused by the therapy with ET1 80CH3 are short-lived and in each case were within a very short time (hours) reversible. UAW often occur in the first two months of therapy and then subside completely. All UAW are always without a pathological correlate.
  • Synthetic lysophospholipids - a new principle of antimetastatic therapy.
  • Taxol - Adverse drug effects according to current specialist information.
  • Taxotere - Adverse drug effects according to current information are also known.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne de la 1-octadécyl-2-méthyl-sn-glycéro-3-phosphocholine (ET180CH3) pour traiter les cancers du sein humains, et la fabrication d'un médicament pour le traitement de ces cancers, le principe actif utilisé étant ET180CH3, lequel est mis sous une forme adaptée à son administration par voie orale dans un excipient liquide.
EP99932780A 1998-07-01 1999-07-01 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (et180ch3) pour traiter les cancers du sein humains Withdrawn EP1091744A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19829448 1998-07-01
DE1998129448 DE19829448A1 (de) 1998-07-01 1998-07-01 1-Octadecyl-2-methyl-sn-glycero-3-phosphocholin (ET180CH3) zur Behandlung von humanen Mammakarzinomen
PCT/EP1999/004563 WO2000001392A1 (fr) 1998-07-01 1999-07-01 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (et180ch3) pour traiter les cancers du sein humains

Publications (1)

Publication Number Publication Date
EP1091744A1 true EP1091744A1 (fr) 2001-04-18

Family

ID=7872671

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99932780A Withdrawn EP1091744A1 (fr) 1998-07-01 1999-07-01 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (et180ch3) pour traiter les cancers du sein humains

Country Status (3)

Country Link
EP (1) EP1091744A1 (fr)
DE (1) DE19829448A1 (fr)
WO (1) WO2000001392A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19959689A1 (de) * 1998-12-04 2000-06-08 Max Delbrueck Centrum Mittel zur Tumortherapie
US7041302B2 (en) * 2001-01-09 2006-05-09 Biother Corporation Therapeutic modulation of the tumor inflammatory response
DE102006019907A1 (de) * 2006-04-28 2007-10-31 Müller-Enoch, Dieter, Prof. Dr. Verwendung von substituierten Glycerinderivaten zur Herstellung einer pharmazeutischen Zubereitung
EP2091520B1 (fr) 2006-11-10 2012-02-22 Alphaptose Gmbh Forme galénique destinée à la voie orale comprenant des composés de glycérol trisubstitués
US20100136029A1 (en) 2006-12-20 2010-06-03 Universitatsklinikum Hamburg-Eppendorf Use of Tri-Substituted Glycerol Compounds for the Treatment of Hematological Malignancies
US8637688B2 (en) * 2006-12-20 2014-01-28 Julia Diederichs Topical dosage form comprising tri-substituted glycerol compounds
WO2013156630A1 (fr) 2012-04-20 2013-10-24 Alphaptose Gmbh Enantiomère s d'un composé glycérol tri-substitué
GB201208850D0 (en) * 2012-05-18 2012-07-04 Alphaptose Gmbh Tri-subsituted glycerol compounds for use in the treatment of clinically isolated syndrome and/or multiple sclerosis

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3941009A1 (de) * 1989-12-12 1991-06-13 Medmark Pharma Gmbh Eliminierung von aktivierten lymphozyten
DE4000084A1 (de) * 1990-01-03 1991-07-04 Medmark Pharma Gmbh Intravenoes applizierbare pharmazeutische zubereitung von et18-och(pfeil abwaerts)3(pfeil abwaerts)
DE4132345A1 (de) * 1991-09-27 1993-04-01 Max Planck Gesellschaft Ether-lysolecithine und alkylphosphocholine in liposomen
KR100381449B1 (ko) * 1994-10-14 2003-07-18 더 리포좀 컴퍼니, 인코퍼레이티드 에테르지질리포좀과이들의제약학적용도
JPH11511130A (ja) * 1995-07-25 1999-09-28 スミスクライン・ビーチャム・コーポレイション ＣｏＡ−非依存性トランスアシラーゼの阻害およびアポトーシス
US5932242A (en) * 1996-10-15 1999-08-03 The Liposome Company, Inc. Ether lipid-containing pharmaceutical compositions and therapeutic uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0001392A1 *

Also Published As

Publication number Publication date
WO2000001392B1 (fr) 2000-02-24
DE19829448A1 (de) 2000-10-12
WO2000001392A1 (fr) 2000-01-13

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