Methods for treating colorectal and metastatic colorectal cancers

a colorectal cancer and metastatic technology, applied in the field of solid tumor treatment, can solve the problems of cell death by apoptosis, achieve the effects of improving overall response rate, reducing disease progression, and stable diseas

Inactive Publication Date: 2019-07-11
ISOFOL MEDICAL AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]The inventors have discovered methods of treating patients diagnosed with colorectal cancer or metastatic colorectal cancers comprising the administration of [6R]-5,10-methylene tetrahydrofolate (6R-MTHF), 5-fluorouracil (5-FU), bevacizumab, and oxaliplatin. These methods surprisingly reduce disease progression, maintain stable disease and provide improved overall response rates compared to standard treatments that utilize folates such as folinic acid.
[0028]In one embodiment, the methods of treating colorectal cancer and metastatic colorectal cancer reduces the size of one or more solid tumors compared to the one or more solid tumors before treatment or compared to “baseline size”, as that term is defined herein. In another embodiment, the methods disclosed herein reduce the size of one or more solid tumors after 2, 4, 8, 16 or 24 weeks of treatment after repeating steps (a) to (f) about every two weeks. In another embodiment, the size of the one or more solid tumors is evaluated by computerized axial tomography (CAT or CT) or magnetic resonance imaging (MRI) at 8, 16, or 24 weeks after repeating steps (a) to (f) about every two weeks.
[0043]In one embodiment, the methods disclosed herein of treating a patient diagnosed with colorectal cancer or metastatic colorectal cancer has an overall response rate (ORR) of at least 40, 50, 60, 70 or 75% after 8 weeks. In another embodiment, the method has an overall response rate (ORR) of at least 40, 50, 60, 70 or 75% after 16 weeks. In yet another embodiment, the methods disclosed herein maintain stable disease between 8 and 16 weeks of treatment.

Problems solved by technology

This in turn leads to suppression of DNA synthesis in the cells, which may lead to cell death by apoptosis.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Clinical Study Design

[0106]A multicenter, randomized, parallel-group, Phase IIb / III study in approximately 440 patients with advanced colorectal cancer is conducted to compare the efficacy of treatment with 6R-MTHF versus LV in combination with 5-FU, oxaliplatin, and bevacizumab.

[0107]This is a randomized, multicenter, parallel-group, Phase IIb / III study to compare the efficacy of arfolitixorin versus LV in patients with advanced CRC treated by 5-FU, oxaliplatin, and bevacizumab.

[0108]Patients will be randomized in a 1:1 ratio to either the investigational arm (arfolitixorin) or the comparator arm (Leucovorin), following the completion of all screening assessments and after confirmation of their eligibility, using a stratified permuted block randomization. Randomization will be stratified for the following baseline factors:[0109]Geographic region (Europe / North America)[0110]Primary tumor location (left colon / right colon / rectal cancer)[0111]Previous adjuvant CRC treatment

[0112]All pa...

example 2

Treatment of Patient Diagnosed with Colorectal Cancer

[0188]An 81-year old female (71 kg; 155 cm) was diagnosed with stage IV metastatic colorectal cancer by PET / CT scan. Colorectal adenocarcinoma was verified by biopsy obtained by sigmoidectomy. Three solid tumors (baseline (prior to treatment) CT measurements: 25, 13 and 12 mm) were identified in the abdomen. The patient had previously been treated for colorectal cancer with eloxatin, which had been discontinued prior to the treatment disclosed here.

[0189]The patient received treatment comprising the administration of bevacizumab, oxaliplatin, 5-FU and 6R-MTHF as a second-line therapy. Bevacizumab was administered at a dose of 5 mg / kg by intravenous infusion over 30 to 90 minutes. Following administration of bevacizumab, oxaliplatin was administered at a dose of 85 mg / m2 by intravenous infusion between 15 and 120 minutes. Following oxaliplatin administration, 5-fluorouracil (5-FU) at a dose of 400 mg / m2 was administered by intraven...

example 3

Treatment of Patient Diagnosed with Colorectal Cancer

[0191]A 48-year old female (67 kg; 160 cm) was diagnosed with stage IV metastatic colorectal cancer by surgery. Colorectal adenocarcinoma was verified by biopsy obtained by masectomy. Two solid tumors (baseline (prior to treatment) CT measurements: 10 and 16 mm) were identified in the liver and lung. The patient had previously been treated for colorectal cancer with bevacizumab, which had been discontinued prior to the treatment disclosed here.

[0192]The patient received treatment comprising the administration of bevacizumab, oxaliplatin, 5-FU and 6R-MTHF as a second-line therapy. Bevacizumab was administered at a dose of 5 mg / kg by intravenous infusion over 30 to 90 minutes. Following administration of bevacizumab, oxaliplatin was administered at a dose of 85 mg / m2 by intravenous infusion between 15 and 120 minutes. Following oxaliplatin administration, 5-fluorouracil (5-FU) at a dose of 400 mg / m2 was administered by intravenous b...

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Abstract

The present invention provides methods for treating patients diagnosed with colorectal cancer and metastatic colorectal cancers in a chemotherapeutic regimen comprising the administration of [6R]-5,10-methylene tetrahydrofolate (6R-MTHF), 5-fluorouracil (5-FU), bevacizumab, and oxaliplatin. The methods reduce disease progression and provide improved overall response rates compared to standard treatments with other folates such as folinic acid.

Description

[0001]The instant application claims priority to EP17187682.4 filed Aug. 24, 2017, PCT / EP2018 / 050274 filed Jan. 5, 2018, U.S. Provisional Application Ser. No. 62 / 651,910 filed Apr. 3, 2018, and U.S. Provisional Application Ser. No. 62 / 769,289 filed Nov. 19, 2018, which are incorporated herein by reference in their entirety. All patents, printed publications and references cited herein are hereby incorporated by reference in their entireties.FIELD OF THE INVENTION[0002]The present invention relates to the treatment of solid tumors in humans diagnosed with colorectal cancer and metastatic colorectal cancers in a chemotherapeutic regimen comprising the administration of [6R]-5,10-methylene tetrahydrofolate (6R-MTHF), 5-fluorouracil (5-FU), bevacizumab, and oxaliplatin.BACKGROUND OF THE INVENTION[0003]Patients diagnosed with colorectal cancer (CRC) or metastatic colorectal cancers (mCRC) are usually treated surgically and, in most circumstances, with curative intent. Surgery, in fact, r...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/574C12Q1/6886C07K16/28
CPCG01N33/57419C12Q1/6886C07K16/2863C12Q2600/158A61K39/39558A61K2039/505A61K39/3955A61K31/4745A61K31/513A61P35/00A61K31/282A61K31/4545A61K31/519A61K2300/00A61K2039/545A61K31/525A61K9/0019A61K39/00
Inventor GANLOV, KARINOSTBERG, MAGNUSLINDBERG, PER L.
Owner ISOFOL MEDICAL AB
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