Eribulin Mesylate Sequential Therapy for Metastatic Breast Cancer

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Solution Overview

Problem

Current cancer treatments for metastatic breast cancer often require systemic approaches with chemotherapeutic drugs that have limitations in determining the extent of metastasis and achieving optimal therapeutic outcomes.

Innovation Solution

The administration of eribulin mesylate prior to other agents like capecitabine, paclitaxel, or carboplatin shows improved antitumor effects, with methods involving sequential administration to enhance treatment efficacy, including reducing cancer cell numbers, tumor volume, and metastasis, and extending survival time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If systemic chemotherapy is used to treat metastatic breast cancer, then the treatment can address undetected metastases, but the therapeutic outcome is limited due to inability to determine extent of metastasis and drug resistance

Engineering Contradiction:
Improvetherapeutic outcomeVSAvoidextent of metastasis
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

The patent applies preliminary action by administering eribulin before other chemotherapeutic agents in a sequential combination therapy regimen. This pre-treatment with eribulin sensitizes cancer cells to subsequent therapies, improving overall therapeutic outcome despite incomplete information about metastasis extent. The sequential administration pattern (eribulin first, then other agents) embodies this principle by preparing the tumor microenvironment for enhanced response to subsequent treatments.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If single-agent chemotherapy is used, then the treatment regimen is simple, but the antitumor effect is insufficient and cancer cells develop resistance

Engineering Contradiction:
Improveantitumor effectVSAvoidtreatment regimen
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges multiple chemotherapeutic agents into a sequential combination regimen, specifically combining eribulin with other agents such as capecitabine, taxanes, or platinum-based drugs. This combination approach enhances antitumor effect through synergistic or additive mechanisms while managing complexity through structured sequential administration protocols. The merging of different drug mechanisms (eribulin's halichondrin B structure with other agent classes) addresses drug resistance and improves efficacy.

Inventive Principle:
Principle #5Merging (Combining)

3Reliability

If combination therapy with multiple agents is used, then the antitumor effect is enhanced, but the treatment complexity and administration schedule become more complex

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidadministration schedule
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent segments the combination therapy into distinct sequential phases: first administering eribulin, then followed by other chemotherapeutic agents at defined intervals. This segmentation of the treatment regimen into manageable temporal segments simplifies the administration schedule despite using multiple agents. The structured sequencing (eribulin followed by specific intervals and then other agents) makes the complex combination therapy more operationally feasible while maintaining enhanced therapeutic efficacy.

Inventive Principle:
Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The combination therapy of eribulin with other agents demonstrates synergistic or additive effects, leading to reduced tumor growth, increased tumor regression rates, and prolonged disease-free and overall survival in patients with metastatic breast cancer.

Implementation Method 1

Halichondrin B has been shown to inhibit tubulin polymerization, microtubule assembly, betas-tubulin crosslinking, GTP and vinblastine binding to tubulin, and tubulin-dependent GTP hydrolysis in vitro.

Methodology Applied
Scientific EffectTubulin polymerization inhibition:

Implementation Method 2

Halichondrin B has been shown to inhibit tubulin polymerization, microtubule assembly, betas-tubulin crosslinking, GTP and vinblastine binding to tubulin, and tubulin-dependent GTP hydrolysis in vitro.

Methodology Applied
Scientific EffectGTP hydrolysis inhibition:

Data Source

PatentEP3148526B1Use of eribulin in the treatment of cancer
Publication Date: 2021.01.06 EISAI R&D MANAGEMENT CO LTD
  • EP3148526B1 patent drawingFigure 1
  • EP3148526B1 patent drawingFigure 2
  • EP3148526B1 patent drawingFigure 3(A)~3(B)

AI summary

The invention features methods and kits for use in treating cancer in a patient in need thereof by administering eribulin or a pharmaceutically-acceptable salt thereof (e.g., eribulin mesylate) prior to a second agent.