Response to Letter: Cost Implications of Reactive Versus Prospective Testing for Dihydropyrimidine Dehydrogenase Deficiency in Patients With Colorectal Cancer: A Single-Institution Experience

We would like to thank you for the opportunity to respond to the questions posed by Dr Bamat as well as thank him and his team for their interest in our article.

Dr Bamat queries the timing of onset of grade 3 or 4 toxicity in our patient population, and seeks more data on several factors that may have contributed to toxicity in patients who are wild-type for the DPYD gene as well as asking about other causative mutations. Additionally, he was interested in the types of toxicity.

Here, we try and answer some of these important questions;

Of the 30 patients in our cost analysis study, data was available for 25 patients who had 5FU toxicity; 9 patients were “early onset,” that is, toxicity occurred after 1 cycle of 5FU and 16 patients were “cumulative onset,” that is, toxicity occurred following 2 or more cycles of 5FU.

In patients who did not have a discernible DPYD mutation (n = 20):

• Age in years (range = 51-80, mean = 66.1, median = 65.5)

• Renal function grade (grade 1 = 13 patients, grade 2 =4 patients, grade 3A = 1 patients, grade 3B = 2 patients). Estimated glomerular filtration rate when not available on biochemistry reports was calculated according to creatinine levels prechemotherapy, age, gender, and ethnicity.

• Body mass index (range = 18.32-33.92, mean = 25.22, median = 24.9). Data not available for all patients (n = 12).

These patients were not tested for mutations in other genes associated with 5FU toxicity namely TYMS, MTHFR and CDA. We have published some data from a subsequent set of patients on the importance of these genes in predicting 5FU toxicity previously (Peoples et al Proc ASCO 2016 e13018).

Toxicity types: DPYD mutant v wild-type

• In the 5 patients who were DPYD mutant;

• In the 20 patients who were DPYD wild-type;

As per above one patient in this data set had cardiotoxicity—early onset coronary vasospasm.

I hope this information is of benefit to you in your future 5FU toxicity research.