Glufosfamide combination therapies for cancer

A technology of glufosfamide and therapy, applied in the field of combined administration of glufosfamide and SGLT2 inhibitory drugs, can solve problems such as toxic effects, kidney damage, restriction and the like

Inactive Publication Date: 2015-01-07
ELEISON PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This causes a toxic effect, or nephrotoxicity, that can severely damage the kidneys, limiting the amount of drug that can be tolerated

Method used

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Examples

Experimental program
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Effect test

example 1

[0078] Patients with pancreatic cancer were given an oral dose of dapagliflozin (SGLT2 inhibitor) at least two hours before starting the intravenous dose of glufosfamide on Day 1 to induce complete suppression of SGLT2 function in the kidney. The usual dose of glufosfamide alone would be 4500 mg / m 2 Glufosfamide was administered over a six hour period every 21 days. However, under the protective effect of SGLT2 blocking drugs, the tolerated dose was much higher, that is, 6000 mg / m given every 3 weeks (or more frequently) 2 or up to 12,000mg / m 2 . Carefully monitor renal function in all patients. These higher or more frequent doses can be tolerated without renal side effects as long as the SGLT2 drug is effective. Therefore, the drug is more effective against pancreatic cancer or other types of cancer. At higher doses, and in the absence of nephrotoxicity, glufosfamide is more likely to cause cancer regression or stabilization, which is clinically beneficial.

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Abstract

The invention provides compositions and methods for treating cancer with glufosfamide in combination with an inhibitor of sodium-glucose transporter type 2 (SGLT2) to block the uptake of glucose in the proximal tubules of the kidneys to decrease renal toxicity. The invention relates to the fields of biomedicine, pharmacology, and molecular biology.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Patent Application Serial No. 61 / 687,114, filed April 19, 2012, which is incorporated herein by reference. technical field [0003] The present invention generally relates to methods for increasing the therapeutic index of a glucose-conjugated drug, such as glufosfamide, by reducing the therapeutic index of the glucose-conjugated drug in the renal tubules using co-administration of a glucose reuptake inhibitor. nephrotoxicity to achieve. Blocking glucose reabsorption with SGLT2 inhibitors reduces the nephrotoxicity of glufosfamide, thereby making it more effective in treating cancer because higher doses can be administered, or effective doses can be associated with lower toxicity. In particular, the present invention relates to the administration of glufosfamide in combination with an SGLT2 inhibitory drug. The present invention relates to the fields of biomedicine, p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01N43/04A61K31/70
CPCA61K31/7034A61K31/7024A61P35/00A61P43/00A61K2300/00
Inventor 埃德温·J·托马斯马修·帕里斯福利斯特·H·安东尼
Owner ELEISON PHARMA
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