5-FU TDM as valuable option to reduce toxicity in daily practice

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Here is a very recent French study using 5-FU TDM in clinical practice for gastric cancers, including pancreatic and stomach, as well as colorectal cancer; in both metastatic and adjuvant settings. All the regimens were 5-FU based and included, in addition to FOLFOX, FOLFIRINOX and FOLFIRI. With a range of cancer types, settings and regimens, this work confirms earlier reports: 1) dosing by BSA results in the majority of patients outside the target 5-FU range, 2) 5-FU levels can be adjusted into target range, and 3) despite increases in dose, toxicities go down.

Morawska K, Goirand F, Marceau L, et al. 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer. Oncotarget. 2018;9(14):11559-11571

 

This article is freely www.oncotarget.com

 

• French group follow-up to Gamelin’s work (1996, 2008) using modern regimens in daily clinical practice

 

• Prospective, single arm study with 155 patients who were dosed in the first cycle by BSA and thereafter by TDM for 2 cycles (3 cycles total)

 

• Target range was 18 – < 28; the algorithm is based on two Gamelin papers and is more aggressive than others i.e. dose adjustments of > 30%
     • It is not clear how the more aggressive dose increases impacted physicians’ agreement. In the Wilhelm study, that limited dose adjustment to 30%, agreement with recommended dose adjustments was high.

 

• Measured by HPLC

 

• Results showed again that:
     • Dosing by BSA does not control inter-patient variability
     • Patients could be adjusted into the therapeutic range
     • In cycle 1 when patients (8/10) suffered > grade 2 toxicity the bolus dose was reduced if the infusional 5-FU was below or in the reference range
             • Point: patients in the therapeutic range or below it, can suffer toxicity from the bolus
     • Higher incidence of grade I/II (19% vs. 41%) or III/IV (8% vs. 15%) according to below/in or above target range. Only grade I/II was statistically significant.
     • Significantly lower toxicities in cycle 3, following two cycles of TDM, than in cycle 1
     • PFS was evaluated only in mCRC, median PFS was not statistically different. There was a trend towards longer PFS for patients who had all cycles in the therapeutic range or above, compared to those with at least one cycle below.

 

• Of interest:
     • Only 60% of the patients had colorectal cancer. Like the German registry study there were patients with pancreatic and stomach cancer (among others).
     • They looked at intra-patient variability by dose adjusted AUC; the CV was 17%, meaning low enough to make TDM practicable.