EP0661977A1 - Treatment of colorectal cancer - Google Patents
Treatment of colorectal cancerInfo
- Publication number
- EP0661977A1 EP0661977A1 EP92916470A EP92916470A EP0661977A1 EP 0661977 A1 EP0661977 A1 EP 0661977A1 EP 92916470 A EP92916470 A EP 92916470A EP 92916470 A EP92916470 A EP 92916470A EP 0661977 A1 EP0661977 A1 EP 0661977A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- course
- therapy
- hydroxy
- day
- topotecan
- 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- Withdrawn
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
- A61K31/33—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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- This invention relates to a method of treating colorectal 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 eukaiyotic 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 ⁇ . 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.
- This invention relates to a method of treating colorectal 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 colorectal 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, filed November 2, 1988, in view of the Notice of Allowability mailed October 12, 1990, 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.
- 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;
- Topotecan is the most preferred compound of the water soluble 10 camptothecin analog class.
- Topotecan as used herein is meant the compound of the foimula:
- Topotecan is water-soluble by virtue of the presence of the basic side-
- topotecan examples include the hydrochloride salt, acetate salt and methanesulfonic 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.
- This invention relates to a method of treating colorectal 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.
- One preferred aspect of this invention relates to a method of treating colorectal cancer in a human afflicted therewith which comprises administering to such human an effective amount of topotecan.
- colonal cancer as used herein is meant adenocarcinoma of the colon and/or rectum.
- treating colorectal cancer is meant the inhibition of the growth of colorectal cancer cells.
- such 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.
- Most preferably such therapy is initiated promptly after surgical ablation of visible colorectal cancer.
- administering is meant parenteral or oral administration.
- parenteral is meant intravenous, subcutaneous and intramuscular administration.
- an 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 colorectal 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 optimal course of therapy for a given set of conditions can be ascertained by those skilled in the art using conventional course of therapy determination tests in view of the information set out herein, as well as the information outlined in U.S. Patent Number 5,004,758. The same information is found in European Patent Application Number 88311366.4, published on June 21, 1989 as Publication Number EP 0321 122.
- the course of therapy generally employed is from about
- the course of therapy employed is from about
- 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.
- the parenteral administration will be by short (e.g., 30 minute) or prolonged (e.g., 24 hour) intravenous infusion. More preferably, the topotecan will be administered by a 30 minute intravenous infusion.
- an additional 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
- the course of therapy employed is from about
- 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: How supplied - As a vial containing 5 mg (of the base) with 100 mg mannitol. The pH is adjusted to 3.0 with HCl NaOH. Lyophilized powder is light yellow in color. Intact vials should be stored under refrigeration (2-8 degrees Centigrade).
- 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.
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)
- Steroid Compounds (AREA)
Abstract
A method of treating colorectal 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.
Description
TREATMENT OF COLORECTAL CANCER
BACKGROUND OF THE INVENTION
This invention relates to a method of treating colorectal 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 eukaiyotic 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 π. 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.
Therefore, there is a need for topoisomerase I inhibiting agents which avoid the aforementioned undesirable features of camptothecin and related
STITUTE SHEET
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.
SUMMARY OF THE INVENTION This invention relates to a method of treating colorectal 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 colorectal cancer in a human afflicted therewith which comprises administering to such human an effective amount of topotecan.
DETAILED DESCRIPTION OF THE INVENTION By the term "a compound of the water soluble camptothecin analog class" is meant any compound claimed in U.S. Patent Number 5,004,758, filed November 2, 1988, in view of the Notice of Allowability mailed October 12, 1990, 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 Publication Number EP 0321 122, the entire disclosure of which is hereby incorporated by reference. Preferred compounds of the water soluble camptothecin analog class include those compounds of the formula:
wherein: a) 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;
~~i e) X is hydroxy and R is N,N-dimethylaminoethyloxymethyl; f) X is hydroxy and R is cyclopropylaminomethyl; 5 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. Topotecan is the most preferred compound of the water soluble 10 camptothecin analog class. By the term "topotecan" as used herein is meant the compound of the foimula:
15 (S)-9-dimethylaminomethyl- 10-hydroxycamptothecin and any pharmaceutically acceptable salt, hydrate or solvate thereof. Topotecan's chemical name is (S)-10[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-lH- pyrano[3',4':6,7]indolizino[l,2-b]quinolone-3,14(4H,12H)-dione.
Topotecan is water-soluble by virtue of the presence of the basic side-
20 chain at position 9 which forms salts with acids. Preferred salt forms of topotecan include the hydrochloride salt, acetate salt and methanesulfonic 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.
The preparation of topotecan (including pharmaceutically acceptable
25 salts, hydrates and solvates thereof) as well as the preparation of oral and parenteral pharmaceutical compositions comprising topotecan 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 Publication Number EP 0321
30 122.
This invention relates to a method of treating colorectal 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. One preferred aspect of this invention relates to a method of treating colorectal cancer in a human afflicted therewith which comprises administering to such human an effective amount of topotecan.
By the term "colorectal cancer" as used herein is meant adenocarcinoma of the colon and/or rectum.
By the term "treating colorectal cancer" as used herein is meant the inhibition of the growth of colorectal cancer cells. Preferably such treatment also leads to the regression of tumor growth, i.e,, the decrease in size of a measurable tumor. Most preferably, such treatment leads to the complete regression of the tumor. Most preferably such therapy is initiated promptly after surgical ablation of visible colorectal cancer. By the term "administering" is meant parenteral or oral administration. By "parenteral" is meant intravenous, subcutaneous and intramuscular administration.
By the term "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 colorectal 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 optimal course of therapy for a given set of conditions can be ascertained by those skilled in the art using conventional course of therapy determination tests in view of the information set out herein, as well as the information outlined in U.S. Patent Number 5,004,758. The same information is found in European Patent Application Number 88311366.4, published on June 21, 1989 as Publication Number EP 0321 122. For parenteral administration of a compound of the water soluble camptothecin analog class, the course of therapy generally employed is from about
2 0.5 to about 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
2 1.0 to about 2.5 mg m of body surface area per day for about five consecutive days. Most preferably, the course of therapy employed is from about 1.5 to about 2
2 mg/m of body surface area per day for about five consecutive days. Preferably, 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. Preferably, the parenteral administration will be by short (e.g., 30 minute) or prolonged (e.g., 24 hour) intravenous infusion. More preferably, the topotecan will be administered by a 30 minute intravenous infusion.
At this time, it is believed that the most preferred course of parenteral therapy to be employed with topotecan for a previously non-treated or lightly
2 pretreated patient is an initial course of therapy of 1.5 mg of topotecan/m of body surface area per day administered by short intravenous infusion for five consecutive days. When the patient has recovered sufficiently from the drug-related effects of
2 this initial course, an additional course of therapy of 2.0 mg of topotecan m of body surface area per day is administered by short intravenous infusion for five consecutive days, to be repeated based on tumor response.
At this time, it is believed that the most preferred course of parenteral therapy to be employed with topotecan for a heavily pretreated patient is an initial
2 course of therapy of 1.0 mg of topotecan/m of body surface area per day administered by short intravenous infusion for five consecutive days. When the patient has recovered sufficiently from the drug-related effects of this initial course,
2 an additional 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.
For oral administration of a compound of the water soluble camptothecin analog class, the course of therapy generally employed is from about
2 1.0 to about 50.0 mg m of body surface area per day for about one to five consecutive days. More preferably, the course of therapy employed is from about
2 1.5 to about 5.0 mg/m of body surface area per day for about five consecutive days. Preferably, 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.
Clinical Pharmaceutical Information Topotecan is currently undergoing Phase I clinical investigation. The following pharmaceutical information is being supplied to the clinicians:
How supplied - As a vial containing 5 mg (of the base) with 100 mg mannitol. The pH is adjusted to 3.0 with HCl NaOH. Lyophilized powder is light yellow in color. Intact vials should be stored under refrigeration (2-8 degrees Centigrade).
Solution Preparation -When the 5 mg vial is reconstituted with 2 ml of Sterile Water for Injection, USP, each ml will contain 2.5 mg of topotecan as the base and 50 mg of mannitol, USP. Topotecan must not be diluted or mixed with buffered solutions because of solubility and stability considerations.
Stability - Shelf life surveillance of the intact vials is ongoing. Because the single-use lyophilized dosage form contains no antibacterial preservatives, it is advised that the reconstituted solution be discarded eight hours after initial entry into the vial. Futher dilutions of the reconstituted solution to concentrations of 0.02 mg ml and 0.1 mg.ml in 5% Dextrose Injection, USP, ("D5W") or 0.9% Sodium Chloride Injection, USP, ("NS") in plastic bags stored at room temperature yielded the following stability results:
Percentage of Initial Topotecan Remaining in Solution
Concentration Piføent
0.02 mg/ml 0.1 mg/ml
D5W 0 100.00 100.00 6 99.29 99.68
24 102.30 98.16 48 101.98 97.91
NS 0 100.00 100.00 6 98.58 97.71
24 96.01 98.30 48 102.03 98.35
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.
Utility One human patient with adenocarcinoma of the colon, who was refractory to previous standard therapy for colon cancer, received a course of
2 therapy comprising intravenous administration of 1.5 mg of topotecan/m of body surface area by continuous iv infusion over a 24 hour period. This course of therapy has been repeated weekly at least four more times to date, and at least a fifty percent
(50%) tumor size regression has been observed, and this regression has lasted at least four weeks.
Claims
1. A method of treating colorectal cancer in a human afflicted therewith which comprises administering to such human an effective amoimt of a compound of the formula:
wherein: a) 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^T-dimethylaminoethyloxymethyl; f) X is hydroxy and R is cyclopropylaminomethyl; g) X is hydroxy and R is morpholinomethyl; h) X is hydroxy and R is aminomethyl; i) X is hydroxy and R is cyanomethyl; or j) X is hydroxy and R is dimethylaminomethyl.
2. The method of Claim 1 wherein the colorectal cancer is adenocarcinoma of the colon.
3. The method of Claim 1 wherein the colorectal cancer is adenocarcinoma of the rectum.
4. The method of Claim 1 wherein the administration is oral.
5. The method of Claim 1 wherein the administration is parenteral.
6. The method of Claim 5 wherein the course of therapy employed is
2 from about 0.5 to about 25.0 mg/m of body surface area per day for about one to about five consecutive days.
7. The method of Claim 6 wherein the course of therapy employed is
2 from about 1.0 to about 2.5 mg/m of body surface area per day for about five consecutive days.
8. The method of Claim 7 wherein the course of therapy employed is 2 from about 1.5 to about 2 mg/m of body surface area per day for about five consecutive days.
9. The method of Claim 6 wherein the course of therapy is repeated at least once at about a seven day to about a twenty-eight day interval.
10. The method of Claim 7 wherein the course of therapy is repeated at least once at about a seven day to about a twenty-eight day interval.
11. The method of Claim 8 wherein the course of therapy is repeated at least once at about a seven day to about a twenty-eight day interval.
12. The method of Claim 4 wherein the administration is via short or long intravenous infusion.
13. The method of Claim 12 wherein the administration is via a 30 minute intravenous infusion.
14. The method of Claim 12 wherein the administration is via a 24 hour intravenous infusion.
15. The method of Claim 5 wherein the course of therapy employed
2 is from about 1.0 to about 50.0 mg/m of body surface area per day for about one to about five consecutive days.
16. The method of Claim 15 wherein the course of therapy employed
2 is from about 1.5 to about 5.0 mg/m of body surface area per day for about five consecutive days.
17. The method of Claim 15 wherein the course of therapy is repeated at least once at about a seven day to about a twenty-eight day interval.
18. The method of Claim 16 wherein the course of therapy is repeated at least once at about a seven day to about a twenty-eight day interval.
19. The method of Claim 1 wherein the compound is topotecan.
20. The method of Claim 12 wherein the compound is topotecan.
EET
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80457091A | 1991-12-10 | 1991-12-10 | |
| US804570 | 1991-12-10 | ||
| PCT/US1992/006131 WO1993011770A1 (en) | 1991-12-10 | 1992-07-24 | Treatment of colorectal cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0661977A4 EP0661977A4 (en) | 1994-10-20 |
| EP0661977A1 true EP0661977A1 (en) | 1995-07-12 |
Family
ID=25189304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP92916470A Withdrawn EP0661977A1 (en) | 1991-12-10 | 1992-07-24 | Treatment of colorectal cancer |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0661977A1 (en) |
| JP (1) | JPH07501818A (en) |
| AU (1) | AU2394392A (en) |
| CA (1) | CA2125293A1 (en) |
| MX (1) | MX9205766A (en) |
| PT (1) | PT100948A (en) |
| WO (1) | WO1993011770A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5552154A (en) | 1989-11-06 | 1996-09-03 | The Stehlin Foundation For Cancer Research | Method for treating cancer with water-insoluble s-camptothecin of the closed lactone ring form and derivatives thereof |
| ES2301590T3 (en) * | 1993-01-15 | 2008-07-01 | The Stehlin Foundation For Cancer Research | USE OF WATER INSOLUBLE CAMPTOTECHINE IN THE FORM OF A CLOSED LACTONE RING FOR THE OBTAINING OF A MEDICINAL PRODUCT FOR THE TREATMENT OF COLON CANCER. |
| US6291425B1 (en) * | 1999-09-01 | 2001-09-18 | Guilford Pharmaceuticals Inc. | Compounds, methods and pharmaceutical compositions for treating cellular damage, such as neural or cardiovascular tissue damage |
| ES2371171B1 (en) * | 2010-06-08 | 2012-11-16 | Consejo Superior De Investigaciones Científicas (Csic) | CAMPTOTECHINE DERIVATIVES AS ANTITUMOR AGENTS. |
| CN102477042A (en) * | 2010-11-26 | 2012-05-30 | 复旦大学 | 10-hydroxyamptothecin derivative, and its preparation method and application |
| CN102659800B (en) * | 2012-05-11 | 2014-09-03 | 中国药科大学 | Hypoxia-activated antitumor compounds and application thereof |
| CN103113381B (en) * | 2013-02-26 | 2014-12-10 | 大连理工大学 | Serial water-soluble hydroxycamptothecine naphthenic amino alcohol derivative and preparation method and use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0321122A2 (en) * | 1987-12-01 | 1989-06-21 | Smithkline Beecham Corporation | Water soluble camptothecin analogs |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0641161B2 (en) * | 1988-02-17 | 1994-06-01 | 積水化成品工業株式会社 | Method for producing styrene resin foam sheet and styrene resin foam sheet for thermoforming |
| JPH0768403B2 (en) * | 1988-12-15 | 1995-07-26 | 東洋エンジニアリング株式会社 | Method of manufacturing foam |
| JP2756366B2 (en) * | 1990-11-27 | 1998-05-25 | 松下電工株式会社 | Method for producing hydrophobic airgel |
-
1992
- 1992-07-24 CA CA002125293A patent/CA2125293A1/en not_active Abandoned
- 1992-07-24 JP JP5510863A patent/JPH07501818A/en active Pending
- 1992-07-24 WO PCT/US1992/006131 patent/WO1993011770A1/en not_active Application Discontinuation
- 1992-07-24 EP EP92916470A patent/EP0661977A1/en not_active Withdrawn
- 1992-07-24 AU AU23943/92A patent/AU2394392A/en not_active Abandoned
- 1992-10-08 MX MX9205766A patent/MX9205766A/en unknown
- 1992-10-09 PT PT100948A patent/PT100948A/en not_active Application Discontinuation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0321122A2 (en) * | 1987-12-01 | 1989-06-21 | Smithkline Beecham Corporation | Water soluble camptothecin analogs |
Non-Patent Citations (3)
| Title |
|---|
| PROC. AM. ASSOC. CANCER RES. ANNU. MEET., vol.31, no.0, 1990 page 431 H BURRIS ET AL. 'SKF 104864: preclinical studies of a new topoisomerase I inhibitor.' * |
| PROC. AM. ASSOC. CANCER RES. ANNU. MEET., vol.31, no.0, 1990 page 436 M.R. MATTERN ET AL 'Synergistig cell killing by ionizing radiation and topoisomerase I inhibitor SKF 104864.' * |
| See also references of WO9311770A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0661977A4 (en) | 1994-10-20 |
| CA2125293A1 (en) | 1993-06-24 |
| MX9205766A (en) | 1993-06-01 |
| PT100948A (en) | 1994-01-31 |
| JPH07501818A (en) | 1995-02-23 |
| AU2394392A (en) | 1993-07-19 |
| WO1993011770A1 (en) | 1993-06-24 |
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