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Combination cancer therapy with a GST-activated anticancer compound and another anticancer therapy

One compound, another technology, applied in the direction of active ingredients of carbohydrates, active ingredients of heavy metal compounds, drug combinations, etc., can solve the problems of not working, not always working, etc.

Inactive Publication Date: 2005-12-21
TELIK INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0027] Cancer treatments are advancing steadily, but even the best current treatments don't always work and often don't work after treatment, so there is an urgent need to find improved cancer treatments

Method used

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  • Combination cancer therapy with a GST-activated anticancer compound and another anticancer therapy
  • Combination cancer therapy with a GST-activated anticancer compound and another anticancer therapy
  • Combination cancer therapy with a GST-activated anticancer compound and another anticancer therapy

Examples

Experimental program
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Effect test

preparation example Construction

[0069] The preparation methods of these compounds and their derivatives can adopt the methods well known to those of ordinary skill in the art and the methods described in US Patent No. 5,556,942.

[0070] A particularly preferred GST-activated anticancer compound is TLK 286 hydrochloride. (Throughout the specification, the TLK 286 mentioned refers to TLK 286 hydrochloride)

[0071] When used as monotherapy for many cancers including ovarian cancer, breast cancer, non-small cell lung cancer and colorectal cancer, TLK 286 is administered at a dose of 400-1000 mg / m by intravenous injection 2 Body surface area, dosing was once a week and once every three weeks.

[0072] Used with docetaxel (75mg / m 2 ) combined with a combination therapy, given at 3-week intervals at doses of 500, 750, and 960 mg / m 2 The TLK286. When used as a combination therapy (AUC 5 and 6 mg / mL·min) in combination with carboplatin, doses of 500, 750, and 960 mg / m were given at 3-4 week intervals 2 TLK 286...

Embodiment 1

[0117] Example 1: TLK 286 Hydrochloride and Carboplatin

[0118] Human ovarian cancer cell line OVCAR-3 with 4×10 4 Cells / mL were inoculated at a rate of 150 μL / well (well), and adsorbed to the well after 4-5 hours. Then, the diluted compound or solvent control was added at a rate of 50 μL / well. TLK 286 was incubated alone and co-incubated with carboplatin to nearly six times the number of cells, and the developmental capacity of the cells was determined by the Wst-1 assay method in which the metabolism dye Wst-1 was used in plates (Indiana, USA (Roche Diagnostics, Indianapolis, Inc.) and incubate for 1-2 hours. Each multi-well plate was recorded several times at intervals of 30 minutes to ensure the linearity of the assay. The combination of TLK 286 and carboplatin compared with either compound alone resulted in significantly enhanced cytotoxicity in various study designs using fixed and variable ratios. The results can be further analyzed using the Combined Index (CI) me...

Embodiment 2

[0119] Example 2: TLK 286 and Oxaliplatin

[0120] The human colon cancer cell line DLD-1 was used at 4×10 4 Cells / mL were seeded at a rate of 150 μL / well and allowed to attach to the well overnight. Diluted compound or solvent control was then added at a rate of 50 μL / well. TLK 286 was incubated alone and co-incubated with carboplatin to nearly eight times the number of cells, and the developmental ability of the cells was determined by the cell Titer-Glo assay (Promrga, Madison, Wisconsin, USA), according to the assay kit instructions To measure. Combining TLK 286 with oxaliplatin compared with either compound alone resulted in a significant increase in cytotoxicity in a different study design, using equal potency and different ratios. The results can be further analyzed using the Combined Index (CI) method with the "CalcuSyn" program from Biosoft. A CI value less than 1 indicates synergy, equal to 1 indicates additive effect, and greater than 1 indicates antagonism. Th...

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Abstract

The invention discloses a compound cancer treatment method for mammals, especially humans, which is treated by administering a therapeutically effective dose of a GST-activated anticancer compound and a therapeutically effective dose of another anticancer therapy. Pharmaceutical compositions, products and kits for use in the method are disclosed. The use of a GST-activated anticancer compound for the manufacture of a medicament for use in the method is disclosed. Disclosed is a method for enhancing anti-cancer therapy in mammals, especially humans, comprising administering a therapeutically effective amount of a GST-activated anti-cancer compound to the mammal treated with the anti-cancer therapy. The use of GST-activated anticancer compounds for the manufacture of medicaments for use in this method is disclosed. The GST-activated anticancer compound is preferably the compound of US Patent No. 5,556,942, more preferably TLK286, especially the hydrochloride.

Description

technical field [0001] The present invention relates to cancer treatment. Background technique [0002] The purpose of cancer treatment (anticancer therapy) is to prevent cancer cells from multiplying, invading, metastasizing, and ultimately killing their host organism, such as a human or other mammal. Since cell proliferation is a characteristic of many normal cells as well as cancer cells, most anticancer therapies have a toxic effect on normal cells, especially those that multiply rapidly, such as bone marrow cells and mucosal cells. Therefore, the goal of selecting an effective treatment for cancer is to find a therapy that can hinder or control the growth of cancer cells with minimal toxicity to its host. In the most effective therapies, the agents used not only prevent but destroy cancer cells, and protect normal cells sufficiently to restore the host to normal or at least satisfactory vital function and quality of life. Cancer treatment approaches include chemothera...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/282A61K31/337A61K31/475A61K31/5377A61K31/70A61K38/05A61K45/06A61P35/00
CPCA61K31/282A61K31/337A61K31/475A61K31/5377A61K31/70A61K38/05A61K45/06A61P35/00A61P43/00A61K2300/00
Inventor 徐华盖尔·L·布朗史蒂文·R·修詹姆斯·G·凯克
Owner TELIK INC
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