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Treatment for cancer

a technology for cancer and compositions, applied in the field of tumour treatment, can solve the problems of major problems associated with paclitaxel therapy, hinder the ongoing efficacy of paclitaxel treatment, and develop side effects

Inactive Publication Date: 2009-11-19
NEWSOUTH INNOVATIONS PTY LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method for treating tumours in a subject by administering a combination of a taxoid and a benzimidazole carbamate compound. The method has been found to be effective in treating various types of tumours, including those that are insensitive to treatment with other antimitotic drugs. The technical effect of the invention is to provide an improved method for treating tumours that combines the benefits of different drugs and increases the effectiveness of treatment.

Problems solved by technology

However major problems associated with paclitaxel therapy exist.
One of these is toxicity.
The development of tolerance or drug resistance in tumour cells to paclitaxel is also a significant factor hindering the ongoing efficacy of paclitaxel treatment.
To overcome resistance, typically the dosages of paclitaxel administered are increased thus leading to the development of side effects.

Method used

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  • Treatment for cancer
  • Treatment for cancer
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Examples

Experimental program
Comparison scheme
Effect test

example 1

Paclitaxel and Albendazole Administration to Human Ovarian Carcinoma Cells

[0120]Human ovarian carcinoma cell lines OVCAR-3, SKOV-3, 1A9 and 1A9PTX22 were used. OVCAR-3 and SKOV-3 cells were obtained from the American Type Culture Collection (ATCC) and maintained on RPMI medium and McCoy5A medium respectively according to ATCC instructions. 1A9 is a clone of the human ovarian carcinoma cell line, A2780 (Sackett et al., 1997). 1A9PTX22 is a paclitaxel resistant subclone of 1A9 cells, isolated as an individual clone in a single step selection by exposing 1A9 cells to 5 ng / ml paclitaxel in the presence of 5 μg / ml verapamil, a Pgp antagonist (Giannakakou et al., 1997). Cells were maintained in 15 ng / ml paclitaxel and 5 μg / ml verapamil continuously.

[0121]Sulforhodamine B (SRB) colorimetric assay was used to study the effect of albendazole, paclitaxel or their combination on tumour cell cytotoxicity in vitro.

[0122]Cells were harvested from exponential phase cultures by trypsinizabon, count...

example 2

Cross Resistance in Paclitaxel Resistant Cell Line

[0128]Taxoids, such as paclitaxel, are one class of antimitotic drugs that target tubulin. A further well-characterized class of tubulin-binding drugs are the Vinca alkaloids, exemplified by vincristine, vinblastine and vinorelbine. The Vinca alkaloids interfere with a cells ability to properly form the mitotic spindle by preventing the normal polymerization of microtubules. They have importance in the treatment of leukemia, lymphomas, small cell lung cancer, and other malignancies. A third class of anti-tubulin drugs, exemplified by colchicine, is comprised of a structurally diverse collection of small molecules that are related by the fact that all bind to a common site on tubulin known as the colchicine site and prevent the normal polymerization of microtubules.

[0129]As described above in Example 1, the present inventors have shown that the paclitaxel resistant cell line 1A9PTX22 displays increased sensitivity to the antiprolifera...

example 3

Compositions for Treatment

[0131]In accordance with the best mode of performing the invention provided herein, specific preferred compositions are outlined below. The following are to be construed as merely illustrative examples of compositions and not as a limitation of the scope of the present invention in any way.

Example 3(A)

Composition for Parenteral Administration

[0132]A composition for parenteral injection could be prepared to contain 0.05 mg to 5 g of albendazole and 0.05 mg to 5 g of paclitaxel in 10 mls to 2 litres of 0.1-10% carboxymethylcellulose.

[0133]Similarly, a composition for intravenous infusion may comprise 250 ml of sterile Ringer's solution, and 0.05 mg to 5 g of albendazole and 0.05 mg to 5 g of paclitaxel.

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Abstract

The present invention provides methods for the treatment of tumors, comprising administration of an effective amount of at least one taxoid and an effective amount of at least one benzimidazol carbamate compound of formula (I). The invention also provides a method for the treatment of tumors insensitive to one or more anti-mitotic drugs, the method comprising administering an effective amount of at least one benzimidazole carbamate compound of formula (I). Also provide are compositions for carrying out methods of the invention.

Description

TECHNICAL FIELD[0001]The present invention relates generally to methods and compositions for the treatment of tumours.BACKGROUND OF THE INVENTION[0002]Paclitaxel and docetaxel are members of the taxoid family of anti-mitotic drugs widely used as chemotherapeutic agents. Taxoids promote microtubule polymerization and stabilization. Their anti-mitotic properties are derived from their ability to bind tubulin and disrupt microtubule dynamics thereby inducing mitotic arrest and cell death.[0003]Paclitaxel has activity against a broad band of tumour types, including breast, ovarian, lung, head and neck cancers. Paclitaxel also has activity in other malignancies that are refractory to conventional chemotherapy, including previously-treated lymphoma and small cell lung cancers and oesophageal, gastric, endometrial, bladder and germ cell tumours (Mekhail and Markman, 2002; Yamazaki et al., 1998). It is one of the most unique, and successful, chemotherapeutic agents currently used in the cli...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4184A61P35/00A61K31/427
CPCA61K31/4184A61K31/427A61K31/337A61P35/00A61P35/02A61P35/04A61P43/00A61K47/30
Inventor MORRIS, DAVID L.POURGHOLAMI, MOHAMMAD HOSSEIN
Owner NEWSOUTH INNOVATIONS PTY LTD