Azenosertib Intermittent Dosing to Balance Cancer Efficacy and Toxicity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing cancer treatments using continuous dosing regimens of Azenosertib face challenges with toxicity and efficacy, particularly in drug-resistant tumors, and combination therapies with other anti-tumor agents suffer from cumulative toxicity.
Innovation Solution
An intermittent dosing regimen for Azenosertib, characterized by consecutive days of administration followed by days without dosing, increases efficacy and reduces toxicity, allowing for higher drug exposure and improved tolerability, especially when combined with other therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If continuous dosing regimen is used, then drug exposure is maintained, but toxicity increases and efficacy diminishes in drug-resistant tumors
Solution Approach 1:
The patent applies periodic action by implementing an intermittent dosing regimen where Azenosertib is administered on specific days (e.g., days 1-5 or 1-7 of each cycle) followed by drug-free intervals (e.g., days 6-21 or 8-21). This periodic administration pattern maintains therapeutic efficacy while allowing toxic effects to subside during drug-free periods, thereby improving the therapeutic index compared to continuous dosing.
2Reliability
If large doses are administered to increase efficacy, then anti-tumor activity improves, but toxicity increases
Solution Approach 1:
The intermittent dosing regimen allows administration of higher doses during active treatment days to maximize anti-tumor efficacy, while the subsequent drug-free intervals allow toxic effects to resolve. This temporal separation enables dose intensification without proportionally increasing cumulative toxicity.
3Reliability
If combination therapy is used, then efficacy against drug-resistant tumors improves, but cumulative toxicity increases
Solution Approach 1:
The intermittent dosing regimen for Azenosertib when combined with other anti-tumor agents creates temporal windows where Azenosertib is absent, allowing other agents to act without overlapping toxicity. This periodic administration reduces cumulative toxicity while maintaining synergistic efficacy against drug-resistant tumors.
Solution Approach 2:
The dosing cycle is segmented into treatment phases and drug-free phases, allowing different therapeutic agents to be administered at different times within the same cycle. This segmentation reduces overlapping toxic effects while maintaining combined therapeutic benefits.
Data Source
AI summary
Provided herein is, among other things, is a method of treating cancer using an improved intermittent dosing regimen for Azenosertib, or a pharmaceutically acceptable salt thereof, administration to achieve a highly efficacious, safe and tolerable dosing regimen to treat many different types of cancers. In one aspect, the method of treating cancer comprises administering a daily dose of Azenosertib, or a pharmaceutically acceptable salt thereof, (e.g., greater than about 350 mg) in accordance with an improved intermittent dosing cycle, wherein the intermittent dosing cycle comprises one or more dosing weeks with each dosing week comprising between about 2-7 consecutive dosing days and between about 1-7 days without dosing. In some embodiments, the intermittent dosing cycle is repeated wherein the dosing weeks are separated by a break of one, two or more weeks. In some aspects, Azenosertib, or a pharmaceutically acceptable salt thereof, is administered as a combination therapy.