Page 105 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

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dihydropyrimi dine dehydrogenas e (DPYD) polymorphis ms in the Korean population for prediction of 5- fluorouracil- associated toxicity.
Ther Drug Monit 2007;29:190- 6.
ref. 28 – CAP, comb
Salgado J et al. Polymorphis ms in the thymidylate synthase and dihydropyrimi dine dehydrogenas e genes predict response and toxicity to capecitabine- raltitrexed in colorectal cancer.
Oncol Rep 2007;17:325- 8.
ref. 29 – FU, comb
Morel A et al. Clinical relevance of different dihydropyrimi dine dehydrogenas e gene single nucleotide polymorphis ms on 5- fluorouracil tolerance.
Clinical Relevanc e Score: AA
gene act. 1: Clinical Relevanc e Score: AA
Level of evidence score: 3
gene act. 1:CTC-AE 4(2)#
- Very common variants (allele frequency 14-22%) in this Korean group were *5, 1737T>C and 1896T>C. No *2A was found.
- The percentage of patients without SNPs was similar to that in healthy volunteers (9.5% versus 10%).
- There was no significant correlation between specific genotypes and toxic response.
NB: *5 does not have reduced DPD activity.
58 Spanish patients with advanced colon cancer received capecitabine (1000 mg/m2 twice daily for 14 days) and raltitrexed every 3 weeks; screening for *2A (IVS14+1G>A).
1 patient was *1/*2A. This patient developed severe toxicity after the first cycle, after which FU was discontinued and more appropriate chemotherapy was started.
not associated with an in-creased risk for toxic response to 5- FU.”
4
Level of evidence score: 3
gene act. 0-1,5: E gene act. 1:CTC-AE 5(2)#
gene act. 0:CTC-AE 4(2)#
487 French patients (300x *1/*1, 10x *1/c.2846A>T, 8x *1/*2A, 1x -1590C/*2A, 1x *2A/*2A, 6x *1/-1590C, 144x *1/*9A, 15x *9A/*9A, 1x *1/*13) received FU monotherapy (n=168) or one of 4 different FU combination therapies (n=319); dose adjustment from the second cycle based on the FU plasma concentration at the end of the previous infusion (Css); discontinuation of treatment or continuation with individual dose adjustment in the event of grade III/IV toxicity; screening for 22 relevant SNPs, including 9 in all patients *2A (IVS14+1G>A), c.2846A>T, *7 (295-298delTCAT), 1156G>T, *9A (85T>C), *9B (2657G>A), *10 (2983G>T), -1590T>C and *13 (1679T>G)) in 171 patients with or without toxicity. 5 variants were found in the population.
Authors’ conclusion: “Considering the common use of fluoropyrimidines, genetic screening would be highly recommendable for the presence of the DPD gene mutation (IVS14+1G>A) related to toxicity, prior to 5- FU administration.”
Authors’ conclusion: “Pretreatment detection of three DPYD SNPs could help to avoid serious toxic adverse events. This approach is suitable for clinical practice and should be compared or combined with pharmacologic approaches. In the case of dihydropyrimidine
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