FTD/TPI Dosing Regimen for Renal Impairment
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Solution Overview
Problem
Current cancer treatments using the FTD/TPI combination drug are ineffective and associated with severe side effects in patients with severe renal impairment, as the drug is not administered due to increased exposure and adverse events in patients with impaired renal function.
Innovation Solution
Administering a divided dose of 30 to 50 mg/m2/day of the FTD/TPI combination drug, in a molar ratio of 1:0.5, twice to four times a day, orally, to patients with creatinine clearance of 15 to 29 mL/min, following a 5-day consecutive administration and 2-day rest schedule, repeated twice with a 14-day rest period, to achieve anticancer effects while minimizing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the FTD/TPI combination drug is administered to patients with severe renal impairment, then anticancer effect can be achieved, but severe side effects occur due to increased drug exposure
Solution Approach 1:
The patent applies parameter changes by adjusting the dosing parameters (dose amount and administration frequency) based on the patient's renal function. For patients with severe renal impairment (CLcr < 30 mL/min), the dose is reduced to 30-50 mg/m2/day and administered 2-4 times daily, which optimizes the balance between achieving anticancer effect and avoiding severe side effects through controlled drug exposure levels
2Object-affected harmful factors
If the FTD/TPI combination drug is not administered to patients with severe renal impairment, then severe side effects are avoided, but anticancer treatment is lost
Solution Approach 1:
The patent implements dynamics by making the dosing regimen adaptable to individual patient characteristics, specifically renal function. The dosing parameters (frequency and amount) are dynamically adjusted based on the patient's creatinine clearance level, allowing safe administration to severe renal impairment patients while maintaining anticancer efficacy through personalized dosing strategies
3Ease of operation
If the standard dosing regimen is used for patients with impaired renal function, then treatment simplicity is maintained, but drug accumulation and toxicity increase
Solution Approach 1:
The patent applies segmentation by dividing the daily dose into multiple administrations throughout the day (2-4 times daily) for patients with severe renal impairment. This segmented dosing approach prevents drug accumulation by reducing the amount administered at any single time point while maintaining total daily dose effectiveness, thereby reducing toxicity without requiring complex monitoring protocols
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
This approach provides a remarkable anticancer effect while avoiding severe side effects in cancer patients with severe renal impairment, maintaining the drug's efficacy and safety by adjusting the dosing regimen based on renal function.
Implementation Method 1
TPI has inhibitory effect against thymidine phosphorylase. It is known that TPI suppresses the decomposition of FTD by thymidine phosphorylase in the living body, thereby potentiating the antitumor effect of FTD
Implementation Method 2
Trifluridine exhibits an antitumor effect by DNA synthesis inhibition by thymidylate production-inhibiting action and DNA function inhibition by incorporation into DNA
Implementation Method 3
TPI is a renal excretory drug, thus it is theoretically considered that, when the FTD/TPI combination drug is administered to the patients with impaired renal function, exposure to FTD can be increased
Data Source
AI summary
A method for treating cancer in patients with creatinine clearance of 15 mL/min or more and less than 30 mL/min, including dividing a combination drug containing α,α,α-trifluorothymidine (FTD) and 5-chloro-6-[(2-iminopyrrolidine-1-yl)methyl]pyrimidine-2,4(1H,3H)-dione hydrochloride in a molar ratio of 1:0.5, in a dose of 30 to 40 mg/m2/day as FTD-equivalent, into two to four times a day, and orally administering it to the patient.