Combination Therapy with an Antitumor Alkaloid

a technology of antitumor alkaloid and combination therapy, which is applied in the direction of biocide, drug composition, metabolic disorder, etc., can solve the problems of limited efficacy of available treatments for many cancer types, ineffective or intolerable, and invasive cancer, and achieve the effect of potentiating antitumor activity

Inactive Publication Date: 2013-10-10
PHARMA MAR U
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011]The present invention establishes that PM01183 potentiates the antitumor activity of other anticancer agents, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and / or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734 and PM00104. Therefore PM01183 and said other anticancer agents can be successfully used in combination therapy for the treatment of cancer.

Problems solved by technology

In addition, cancer is invasive and tends to infiltrate the surrounding tissues and give rise to metastases.
However, the efficacy of available treatments for many cancer types is limited, and new, improved forms of treatment showing clinical benefits are needed.
This is especially true for those patients presenting with advanced and / or metastatic disease and for patients relapsing with progressive disease after having been previously treated with established therapies which become ineffective or intolerable due to acquisition of resistance or to limitations in administration of the therapies due to associated toxicities.
Unfortunately, more than 50% of all cancer patients either do not respond to initial therapy or experience relapse after an initial response to treatment and ultimately die from progressive metastatic disease.
Unfortunately, none of the current chemotherapies with these agents posses an ideal profile.

Method used

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  • Combination Therapy with an Antitumor Alkaloid
  • Combination Therapy with an Antitumor Alkaloid
  • Combination Therapy with an Antitumor Alkaloid

Examples

Experimental program
Comparison scheme
Effect test

example 1

In Vitro Studies to Determine the Effect of PM01183 in Combination with Chemotherapeutic Agents on Human Lung Carcinoma Cell Lines

[0131]The objective of this study was to determine the ability of PM01183 to potentiate the antitumor activity of chemotherapeutic agents used in the treatment of lung carcinoma.

[0132]The following agents were evaluated in combination with PM01183: oxaliplatin, carmustine, cyclophosphamide, mytomicin C (stock solutions of these compounds prepared in sterile double distilled water and stored at −20° C.), 5-fluorouracil (5-FU), gemcitabine, paclitaxel, docetaxel, vincristine, daunorubicin, actinomycin D, topotecan, etoposide, bortezomib, vorinostat, dacarbazine, temsirolimus, erlotinib, ET-743 and PM00104 (stock solutions of these compounds prepared in pure DMSO and stored at −20° C.). Additional serial dilutions were prepared in serum-free culture medium to achieve a final 4× concentration. Aliquots of 50 μL of each diluted compound were added per well.

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example 2

In Vitro Studies to Determine the Effect of PM01183 in Combination with Chemotherapeutic Agents on Human Sarcoma Cell Lines

[0137]The objective of this study was to determine the ability of PM01183 to potentiate the antitumor activity of chemotherapeutic agents used in the treatment of sarcoma.

[0138]The following agents were evaluated in combination with PM01183: cisplatin, oxaliplatin, cyclophosphamide, mytomicin C (stock solutions of these compounds prepared in sterile double distilled water and stored at −20° C.), gemcitabine, docetaxel, vincristine, vinorelbine, daunorubicin, cytarabine, actinomycin D, topotecan, etoposide, vorinostat, dacarbazine, temsirolimus, erlotinib, aplidine, PM02734, ET-743 and PM00104 (stock solutions of these compounds prepared in pure DMSO and stored at −20° C.). Additional serial dilutions were prepared in serum-free culture medium to achieve a final 4× concentration. Aliquots of 50 μL of each diluted compound were added per well.

A673 was the human rh...

example 3

In Vitro Studies to Determine the Effect of PM01183 in Combination with Chemotherapeutic Agents on Human Malignant Melanoma Cell Lines

[0142]The objective of this study was to determine the ability of PM01183 to potentiate the antitumor activity of chemotherapeutic agents used in the treatment of malignant melanoma.

[0143]The following agents were evaluated in combination with PM01183: cisplatin, mytomicin C (stock solutions of these compounds prepared in sterile double distilled water and stored at −20° C.), 5-fluorouracil, doxorubicin, daunorubicin, cytarabine, topotecan, irinotecan, methotrexate, etoposide, dacarbazine, temsirolimus, PM02734, ET-743 and PM00104 (stock solutions of these compounds prepared in pure DMSO and stored at −20° C.). Additional serial dilutions were prepared in serum-free culture medium to achieve a final 4× concentration. Aliquots of 50 μL of each diluted compound were added per well.

SK-MEL-2 was the human melanoma cell line selected for this assay. SK-MEL...

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Abstract

The present invention relates to the combination of PM01183 with several anticancer drugs, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and/or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734 and PM00104, and the use of these combinations in the treatment of cancer.

Description

FIELD OF THE INVENTION[0001]The present invention relates to the combination of PM01183 with other anticancer drugs, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and / or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734, and PM00104 and the use of these combinations in the treatment of cancer.BACKGROUND OF THE INVENTION[0002]Cancer develops when cells in a part of the body begin to grow out of control. Although there are many kinds of cancer, they all arise from out-of-control growth of abnormal cells. Cancer cells can invade nearby tissues and can spread through the bloodstream and lymphatic system ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4995A61K31/55A61K31/704A61K31/4164A61K31/513A61K31/7068A61K31/4188A61K31/4375A61K31/337A61K33/24A61K33/243
CPCA61K31/4995A61K31/337A61K31/519A61K31/69A61K31/7068A61K45/06A61K31/513A61K31/4164A61K31/4188A61K31/4375A61K31/704A61K31/55A61K38/15A61K33/24A61K2300/00A61K33/243A61P1/04A61P1/16A61P1/18A61P11/00A61P13/08A61P13/10A61P13/12A61P15/00A61P17/00A61P21/00A61P25/00A61P3/00A61P35/00A61P35/02A61P43/00A61K31/34A61K31/395
Inventor MONEO OCANA, VICTORIAN NEZ, GEMA SANTAMARIAGARCIA FERNANDEZ, LUIS FRANCISCOGALMARINI, CARLOS MARIAGUILLEN NAVARRO, MARIA JOSEAVILES MARIN, PABLO MANUEL
Owner PHARMA MAR U
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