Combination comprising combretastatin and anticancer agents

a technology of combretastatin and anticancer agent, which is applied in the direction of heterocyclic compound active ingredients, drug compositions, biocides, etc., can solve problems such as interfering with the reproductive cycle of cells, and achieve the effect of dissociating the toxic

Inactive Publication Date: 2005-04-07
AVENTIS PHARMA SA (US)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The efficacy of the combinations on solid tumors were determined experimentally in the following manner:
The animals subjected to the experiment, generally mice, were subcutaneously grafted bilaterally with 30 to 60 mg of a tumor fragment on day 0. The animals bearing tumors were mixed before being subjected to the various treatments and controls. In the case of treatment of advanced tumors, tumors were allowed to develop to the desired size, and animals having insufficiently developed tumors were eliminated. The selected animals were distributed at random to undergo the treatments and controls. Animals not bearing tumors were also subjected to the same treatments as the tumor-bearing animals in order to be able to dissociate the toxic effect from the s

Problems solved by technology

Alkylating agents such as cyclophosphamide, isosfamide, melphalan, hexamethylmelamine, thiotepa or dacarbazine gene

Method used

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  • Combination comprising combretastatin and anticancer agents
  • Combination comprising combretastatin and anticancer agents
  • Combination comprising combretastatin and anticancer agents

Examples

Experimental program
Comparison scheme
Effect test

example 1

In this and the following examples, RPR 258062A corresponds to the hydrochloride salt of compound IIa. The agents were administered intravenously unless otherwise specified.

IN VIVO EVALUATION OF RPR 258062AAND CISPLATINUMSched-HNTDTu-uleDoseT-CRRAgentmordaysmg / kgdaysLcKPRCRTFSSingle agents:RPR 258062AC5112,16116101.26 / 60 / 60 / 6CDDP12, 166.216.51.95 / 60 / 60 / 6Combination: -simultaneousRPR 258062A12, 16116NANA6 / 66 / 66 / 61stCDDP12, 1610- sequentialRPR 258062A1458515.95 / 55 / 50 / 5CDDP15, 1910

Abbreviations used:

HNTD = highest nontoxic dose;

T-C = tumor growth delay;

LcK = log cell kill;

RR = response rate;

PR = partial response;

CR = complete response,

TFS = tumor free survivors.

Conclusion: The combination of RPR 258062A and cisplatinum is synergistic.

example 2

IN VIVO EVALUATION OF RPR 258062A AND VINORELBINEHNTDScheduleDoseRRAgentTumordaysmg / kgT-C daysLcKPRCRTFSSingle agents:RPR 258062AMA13 / C15, 2515050.50 / 50 / 50 / 5Vinorelbine15, 2519.845.54.65 / 55 / 50 / 5Combination -sequentialRPR 258062A 1st147584.78.5*5 / 55 / 52 / 5Vinorelbine 2nd15, 2532

*log cell kill evaluated on the limited number of mice that developed tumor, the other mice in the group being tumor free survivors.

Abbreviations used:

HNTD = highest nontoxic dose;

T-C = tumor growth delay;

LcK = log cell kill;

RR = response rate;

PR = partial response;

CR = complete response,

TFS = tumor free survivors.

Conclusion: The combination of RPR 258062A and vinorelbine is synergistic.

example 3

IN VIVO EVALUATION OF RPR 258062A AND DOCETAXELScheduleHNTD DoseRRAgentTumordaysmg / kgT-C daysLcKPRCRTFSSingle agents:DocetaxelMA13 / C17, 246826.73.2*6 / 64 / 63 / 6RPR 258062A17, 2424210.81.31 / 61 / 60 / 6(2x / d)Combination -sequentialRPR 258062A16, 2315074.86.0*6 / 66 / 64 / 6(2x / d)Docetaxel17, 24109.6

*log cell kill evaluated on the limited number of mice that developed tumor, the other mice in the group being tumor free survivors.

Abbreviations used:

HNTD = highest nontoxic dose;

T-C = tumor growth delay;

LcK = log cell kill;

RR = response rate;

PR = partial response;

CR = complete response,

TFS = tumor free survivors.

Conclusion: The combination of RPR 258062A and docetaxel is synergistic.

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Abstract

An antitumor combination comprising a stilbene derivative and an anticancer compound selected from the group consisting of taxanes, alkylating agents, antimetabolites, vinca alkaloids, platinum compounds, epidophylloptoxins, and antibiotics as the active ingredients is provided. Methods of using these pharmaceutical preparations for the treatment of solid carcinomas and the like are also provided.

Description

FIELD OF INVENTION The present invention relates to therapeutic combinations comprising a stilbene derivative and anticancer agents such as taxanes, alkylating agents, antimetabolites, vinca alkaloids, epidophylloptoxins, and antibiotics for the treatment for cancer. The invention relates to the treatment of cancers, more especially solid tumors, with associations of stilbene derivatives and other anticancer drugs and the use of such associations for an improved treatment against cancers, and to uses of these effective ingredients for the treatment (therapy), suppression, and amelioration of tumors, and the like. BACKGROUND OF THE INVENTION Today, a wide variety of chemotherapeutic agents are used for treatment, and suppression of tumors, especially malignant solid tumors. Although these agents may have a tumor reducing effect, it is often not possible for these known agents to effect a cure due to acquisition of resistance against the agent by the cancer, relapse of the tumors, ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/09A61K31/135A61K31/167A61K31/337A61K31/47A61K31/475A61K31/704A61K33/243A61K45/06A61P35/00A61P35/04A61P43/00
CPCA61K31/09A61K31/135A61K31/16A61K31/337Y10S514/922A61K31/4745A61K31/7072A61K45/06A61K31/47A61K31/70A61K31/165A61K33/24A61K31/704A61K31/475A61K31/335A61K2300/00A61P35/00A61P35/04A61P43/00A61K33/243A61K31/075A61K31/136
Inventor BISSERY, MARIE-CHRISTINE
Owner AVENTIS PHARMA SA (US)
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