CDK Inhibitor and Antineoplastic Agent Combination for SCCHN
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Solution Overview
Problem
Current treatments for squamous cell carcinoma of the head and neck (SCCHN) often face challenges with high rates of local and distant failure, resistance to conventional antineoplastic agents, and limited therapeutic options, necessitating the development of novel combination approaches with different mechanisms of action.
Innovation Solution
A pharmaceutical combination comprising a cyclin-dependent kinase (CDK) inhibitor selected from specific compounds or their pharmaceutically acceptable salts, in combination with one or more antineoplastic agents such as sorafenib, lapatinib, erlotinib, cisplatin, 5-fluorouracil, or docetaxel, which can be administered simultaneously or sequentially to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antineoplastic agents are used for treatment, then initial therapeutic response may be achieved, but resistance develops and treatment efficacy decreases over time
Solution Approach 1:
The patent combines a CDK inhibitor with conventional antineoplastic agents to create a pharmaceutical composition that addresses drug resistance. The CDK inhibitor targets the resistance mechanism by blocking cell cycle progression, while the conventional agent provides cytotoxic activity, creating a synergistic effect that maintains treatment efficacy over time and prevents resistance development
Solution Approach 2:
The invention creates a composite therapeutic approach by formulating a combination of two distinct pharmacological agents with different mechanisms of action. This composite formulation allows the CDK inhibitor to sensitize cancer cells to the conventional antineoplastic agent, thereby extending the duration of therapeutic response and preventing resistance
2Reliability
If single agent therapy is used, then treatment simplicity is maintained, but therapeutic efficacy is limited and resistance occurs
Solution Approach 1:
The patent merges a CDK inhibitor with conventional antineoplastic agents in a single pharmaceutical composition or coordinated treatment regimen. This combination approach enhances therapeutic efficacy by targeting multiple pathways simultaneously while managing complexity through established administration protocols and dosing schedules
3Reliability
If higher doses of conventional agents are used to overcome resistance, then short-term efficacy improves, but toxicity increases
Solution Approach 1:
The patent utilizes parameter changes by introducing a CDK inhibitor that modifies the cellular response to conventional antineoplastic agents. This allows for dose optimization where lower doses of the conventional agent can achieve the same therapeutic effect when combined with the CDK inhibitor, thereby maintaining efficacy while reducing toxicity
Data Source
AI summary
The present invention relates to a pharmaceutical combination for use in the treatment of squamous cell carcinoma, comprising a CDK inhibitor selected from the compounds of formula (I);or a pharmaceutically acceptable salt thereof and one or more antineoplastic agents selected from sorafenib, lapatinib, erlotinib, cisplatin, 5-fluorouracil, docetaxel or cetuximab or a pharmaceutically acceptable salt thereof. The said pharmaceutical combination exhibits synergy when used in the treatment of squamous cell carcinoma of head and neck (SCCHN). The invention also relates to a pharmaceutical composition comprising the said combination and a method for the treatment of squamous cell carcinoma of head and neck (SCCHN), using a therapeutically effective amount of said combination.