Intermittent FGFR Inhibitor Dosing Reduces Hyperphosphatemia
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Solution Overview
Problem
Current FGFR inhibitors for cancer treatment often cause side effects such as weight loss and increased blood phosphorus levels, which need to be mitigated while maintaining their antitumor efficacy.
Innovation Solution
A 3,5-disubstituted benzene alkynyl compound or its salt is intermittently administered with a dosing interval of at least one day, twice a week, to inhibit FGFR effectively with reduced systemic toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FGFR inhibitor is continuously administered to maintain antitumor efficacy, then tumor growth suppression is improved, but side effects such as weight loss and increased blood phosphorus levels worsen
Solution Approach 1:
The patent applies periodic action by administering the FGFR inhibitor in intermittent cycles rather than continuously. The compound is given at specific intervals (e.g., once weekly, twice weekly, or every other day) to maintain therapeutic effectiveness while allowing physiological recovery periods that reduce side effects like weight loss and hyperphosphatemia.
Solution Approach 2:
The patent employs parameter changes by adjusting the dosing schedule parameters (frequency, interval, duration) of FGFR inhibitor administration. By optimizing these temporal parameters, the treatment maintains adequate drug exposure for tumor suppression while reducing cumulative toxicity and metabolic side effects associated with continuous dosing.
2Reliability
If FGFR inhibitor dosage is increased to enhance antitumor effect, then tumor growth suppression is improved, but systemic toxicity and blood phosphorus levels worsen
Solution Approach 1:
Instead of increasing dosage continuously, the patent uses periodic administration schedules that provide adequate drug levels during treatment windows while allowing phosphorus metabolism to normalize during interruption periods, thereby reducing systemic toxicity and hyperphosphatemia.
Solution Approach 2:
The patent maintains continuous therapeutic pressure on tumor growth through optimized intermittent dosing schedules, ensuring that drug exposure remains sufficient for antitumor efficacy while the intermittent nature allows physiological systems to recover and reduces cumulative toxic effects.
Data Source
AI summary
The problems to be solved by the present invention are to provide a novel FGFR inhibitor that is potent and highly selective, and to provide an antitumor agent with which side effects such as an elevated blood phosphorus concentration are alleviated while maintaining the antitumor effect of the FGFR inhibitor. The present invention provides an antitumor agent comprising a 3,5-di-substituted benzene alkynyl compound represented by general formula (I) or salt thereof, which is used by administering the 3,5-di-substituted benzene alkynyl compound or salt thereof according to an administration schedule of two or more times/week at an administration interval of at least one day between doses.