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OnDose® Study Demonstrates Need for Improved Dosing Approach for Colorectal Cancer Patients

  
  
  
  

I recently wrote about the shortcomings of Body Surface Area (BSA) based dosing of chemotherapy drugs.  A study just published in Clinical Colorectal Cancer has reaffirmed that BSA dosing of 5-fluorouracil for colorectal cancer patients receiving FOLFOX treatment regimens is suboptimal in ensuring that patients are administered the right dose for treatment efficacy. 

This study analyzed the 5-FU plasma concentrations of 357 patients who were dosed based upon BSA. Over 50% of these patients received too little drug to reach the plasma target range and another 28% were above the target range.  Only 21% of patients were found to have drug plasma levels within the target range with BSA dosing.  Prior studies have shown that patients whose plasma drug levels are within target range realize better treatment outcomes and suffer lower toxic side effects associated with chemotherapy drugs. 

Why is there such wide variation in drug plasma concentrations among patients?  BSA dosing is based solely upon body mass and does not take into account the many factors that impact drug metabolism, including age, gender, disease state, drug-drug interactions, genotype and organ function. 

Sixty-two of the patients in the study had their 5-FU doses personalized during the course of treatment to reach the drug plasma target range.  Of these 62, only 5% were within target range at the beginning of the study and over 50% were outliers.  After four rounds of adjusted dosing, 37% were within target and only 14.5% were outliers. 

OnDose®, the simple blood test that enables oncologists to determine whether their patients are being over- or under-dosed is being offered in the United States by Myriad Genetics. 

Adrienne Choma, Vice President, Marketing & Sales

Comments

I continue to be interested in how many TDM measurements should be made optimally given the PK varies and when they should they be made post dose. Is one enough?
Posted @ Sunday, June 12, 2011 7:45 AM by Pete Kissinger
The recommended number of TDM measurements depends upon the drug being monitored. In the case of 5-FU, it is estimated that the average patient will require between 8 and 10 tests during the course of treatment. A patient found to be out of optimal range at initial testing will require 3 to 4 cycles of adjusted dose to achieve optimal plasma drug levels. Thereafter, the patient should be monitored every 2 to 3 cycles ensure that the optimal level is maintained. With changing conditions - such as tumor shrinkage due to positive response to therapy - adjustment of dose may be needed to avoid overdosing and potential increase in toxicity. 
 
 
 
Only one sample per treatment cycle is required to generate a My5-FU test result. Samples are collected during the course of infusion, when the drug achieves steady state in the patient's bloodstream.  
 
 
 
I hope that I have answered your questions.
Posted @ Monday, June 13, 2011 12:18 PM by Adrienne Choma
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