Methods of treating tumors

a tumor and tumor technology, applied in the field of cancer therapy, can solve the problems of high mortality rate, low specificity, chemotherapeutic agents, etc., and achieve the effects of reducing toxicity, prolonging clinical half-life, and improving ability to cross the blood-brain barrier

Inactive Publication Date: 2006-06-22
GEISTLICH PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006] By derivative of taurolidine or taurultam is meant a sulfonamide compound which possesses at least 10% of the neoplastic activity of taurolidine or taurultam, respectively. A sulfonamide compound is one having a R2N—SO2R′ formula. Derivatives of the compounds described herein may differ structurally from a reference compound, e.g., taurolidine or taurultam, but preferably retain at least 50% of the biological activity, e.g., induction of apoptotic cell death, of the reference compound. More preferably, a derivative has at least 75%, 85%, 95%, 99% or 100% of the biological activity of the reference compound. In some cases, the biological activity of the derivative may exceed the level of activity of the reference compound. Derivatives may also possess characteristics or activities not possessed by the reference compound. For example, a derivative may have reduced toxicity, prolonged clinical half-life, or improved ability to cross the blood-brain barrier.

Problems solved by technology

Despite advances in the identification of chemotherapeutic agents for inhibiting the growth of cancer cell, cancer remains a formidable disease with a high mortality rate.
A significant problem of chemotherapeutic agents is low specificity.
Many anticancer agents do not adequately distinguish normal cells from cancer cells.
As a result, they often carry undesirable serious side effects.

Method used

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  • Methods of treating tumors
  • Methods of treating tumors
  • Methods of treating tumors

Examples

Experimental program
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Effect test

example 1

Cytotoxic and Mechanistic Evaluation of Antineoplastic Agents

[0055] Taurolidine was found to be active at inhibiting the growth of a variety of human tumor cell lines in vitro. PA-1 and SKOV-3 human ovarian tumor cell lines and NIH-3T3 murine fibroblasts were used to determine the mechanism of antitumor activity. The studies revealed that this effect was associated with alterations in DNA structure, cell membrane components, and protein cleavage that were consistent with the induction of apoptosis specifically in tumor cells. Antineoplastic evaluation of Taurolidine in nude mice bearing intraperitoneal xenografts of human ovarian tumors demonstrated that this agent significantly inhibited tumor development and growth in vivo.

[0056] To study neoplastic activity, Taurolidine was formulated as 2% solution in 5% Kollidon 17PF. Standard cell culture growth media (e.g., High glucose DMEM, RPMI 1640, McCoy's 5A, and F12K), trypsin, and fetal bovine serum (FBS) were all purchased from GIB...

example 2

Clinical Use

[0083] Taurolidine was administered by i.p. lavage immediately following surgery for removal of recurrent ovarian tumors. For patients with glioblastoma, Taurolidine was administered systemically. To date, Taurolidine has been well tolerated in these patients.

[0084] Four patients, which were diagnosed with advanced recurrent glioblastoma multiforma, were treated with taurolidine. The prognosis for this group of patients was determined to be approximately 8 weeks of survival. Each patient received at least one 5 week regimen in which 20 g of taurolidine was infused intravenously into the arm over a period of 6 hours twice a week. In 3 out of the 4 patients treated, the tumor mass decreased or stayed the same; and in one case, a slight increase was seen. At 14 weeks after the initiation of therapy, each of the patients remains alive, having exceeded the 8 week prognosis. A beneficial clinical effect was achieved in these brain tumor patients with systemic administration ...

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Abstract

The invention provides a method of inhibiting tumor growth in a mammal, by administering to the mammal composition containing taurolidine, taurultam, or a biologically active derivative thereof. The composition is administered to directly contact a tumor cell at a dose sufficient to induce cell death by apoptosis.

Description

RELATED APPLICATION [0001] This application is a continuation of U.S. patent application Ser. No. 1 / 301,263, filed Nov. 21, 2002, now issued as U.S. Pat. No. 6,995,164, which is a continuation of U.S. patent application Ser. No. 09 / 730,666, filed Dec. 6, 2000, now issued as U.S. Pat. No. 6,521,616, which claims priority Under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 60 / 169,122, which was filed on Dec. 6, 1999, U.S. Provisional Application Ser. No. 60 / 169,127, which was filed on Dec. 6, 1999, and U.S. Provisional Application Ser. No. 60 / 169,128, which was filed on Dec. 6, 1999, each of which is hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION [0002] The invention relates to cancer therapy. [0003] Despite advances in the identification of chemotherapeutic agents for inhibiting the growth of cancer cell, cancer remains a formidable disease with a high mortality rate. A significant problem of chemotherapeutic agents is low specificity. Many ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/549A61K9/06C07D233/74A61K9/10A61K9/70A61K9/72A61K31/16A61K31/17A61K31/18A61K31/4166A61K31/505A61K31/522A61K31/54A61K45/00A61K45/06A61P35/00A61P35/02A61P35/04A61P43/00C07D285/08C07D285/18
CPCA61K31/505Y10S514/885A61K31/549A61K45/06A61K31/54Y10S514/908A61K31/541A61K31/00A61K31/16A61K2300/00A61K31/17A61K31/18A61K31/4166A61K31/522A61P1/04A61P1/16A61P1/18A61P11/00A61P13/08A61P13/10A61P15/00A61P17/00A61P25/00A61P35/00A61P35/02A61P35/04A61P43/00
Inventor CALABRESI, PAULDARNOWSKI, JAMES
Owner GEISTLICH PHARMA
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