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Tetrahydrofolates in combination with egfr-inhibitors

A tetrahydrofolate and inhibitor technology, applied in the field of cancer treatment, can solve problems such as cytotoxicity and achieve the effect of less side effects

Inactive Publication Date: 2014-10-22
ISOFOL MEDICAL AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However antifolates and fluoropyrimidines are cytotoxic and can be associated with serious side effects in many patients

Method used

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  • Tetrahydrofolates in combination with egfr-inhibitors
  • Tetrahydrofolates in combination with egfr-inhibitors
  • Tetrahydrofolates in combination with egfr-inhibitors

Examples

Experimental program
Comparison scheme
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Embodiment Construction

[0104] Objective: To determine the antitumor efficacy of the combination of methylene-THF and cetuximab in LoVo, a colorectal adenocarcinoma xenograft model. LoVo is a cell line sensitive to cetuximab and 5-FU.

[0105] Study Design: A total of 50 female NCr nu / nu mice (10 per group) were injected sc in the flank with 1 x 10 7 LoVo tumor cells. After 7 days, according to the schedule in Table 1, they were administered by intraperitoneal injection. Animals were monitored individually. The end point of the experiment is when the tumor weight reaches 1000mm 3 Or 75 days upon arrival, whichever comes first. Respondents can be tracked for longer periods of time. Animals were euthanized when the endpoint was reached. Body weight (g) and tumor volume (mm 3 ) at 1, 2, 3, 4, 5, 7, 11, 14, 18, 21, 25, 28, 32, 35, 39, 42, 46, 49, 53, 56, 60, 63, 70 and 74 day measurement.

[0106] Table 1. Treatment Groups and Dosing

[0107]

[0108]

[0109] biwk = every other week

[...

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Abstract

The present invention relates a pharmaceutical composition comprising and EGFR inhibitor and methylene-tetrahydrofolate, tetrahydrofolate or methyl-tetrahydrofolate, for use in the treatment of cancer. The methylene-tetrahydrofolate, tetrahydrofolate or methyl-tetrahydrofolate enhances the anticancer efficacy of the EGFR inhibitor. The cancers that may be treated include breast cancer, gastric cancer, gastrointestinal cancer, gall bladder cancer, bile duct cancer, colon cancer, rectal cancer, liver cancer, pancreatic cancer, head and neck cancer, esophageal cancer, mesotheolioma cancer, lung cancer including non-small-cell lung cancer, ovarian cancer, endometrial cancer, cervicial cancer, peripheral T-cell lymphoma (PTCL), melanoma, brain tumors, adenocarcinoma, esophageal cancer, and osteosarcoma

Description

field of invention [0001] The present invention relates to the use of EGFR inhibitors and reduced folates for cancer therapy. Background of the invention [0002] Cancer is one of the biggest health problems in the world. It is one of the leading causes of death worldwide, accounting for more than 60% of all deaths worldwide, along with cardiovascular diseases, diabetes, and chronic respiratory diseases. Nearly 12.7 million new cancer cases and 7.6 million cancer deaths occurred worldwide in 2008. [0003] Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. Almost 60% of cases occur in developed regions. Incidence rates vary around the world, but are substantially higher in men than in women overall. More than 600,000 people die from the disease each year, accounting for 8% of all cancer-related deaths. In the United States alone, more than 150,000 new cases are diagnosed each year. Colon cancer is define...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/519A61K39/395A61K45/06A61P35/00
CPCA61K45/06A61K39/3955C07K16/2863A61K2039/505A61K31/44A61K31/4704A61P35/00A61K2300/00A61K31/519A61K39/39558
Inventor 本特·古斯塔夫森比约恩·卡尔松
Owner ISOFOL MEDICAL AB
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