SAFETY MATTERS: THE TROUBLED AND FINALLY SUCCESSFUL STORY OF DIHYDROPYRIMIDINE DEHYDROGENASE PHARMACOGENETIC TEST IN CANCER PATIENTS

2021 ◽  
Vol 01 (01) ◽  
pp. 72
Author(s):  
S. Crucitta ◽  
F. Sciandra ◽  
A. Cerbioni ◽  
F. Cucchiara ◽  
R. Arici ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Dihydropyrimidine Dehydrogenase ◽  
Pharmacogenetic Test

Dihydropyrimidine dehydrogenase activity in cancer patients

1993 ◽  
Vol 29 (5) ◽  
pp. 740-744 ◽  
Author(s):  
G.A. Milano ◽  
M.H. Gaspard ◽  
A. Thyss ◽  
N. Renée ◽  
M. Schneider ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Dehydrogenase Activity ◽  
Dihydropyrimidine Dehydrogenase

Population study of dihydropyrimidine dehydrogenase in cancer patients.

1994 ◽  
Vol 12 (11) ◽  
pp. 2248-2253 ◽  
Author(s):  
M C Etienne ◽  
J L Lagrange ◽  
O Dassonville ◽  
R Fleming ◽  
A Thyss ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Mononuclear Cells ◽  
Dihydropyrimidine Dehydrogenase ◽  
Rare Event ◽  
Systemic Exposure ◽  
Adaptation Strategy ◽  
Large Set ◽  
Carbon 14 ◽  
Dose Adaptation ◽  
A Prospective Study

PURPOSE We conducted a prospective study on a large set of cancer patients in an attempt to evaluate the incidence of complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency as found in peripheral mononuclear cells (PMNC). PATIENTS AND METHODS One hundred eighty-five unselected consecutive cancer patients were included. The population consisted of 152 men (mean age, 62.1 years; range, 35 to 90) and 33 women (mean age, 59.2 years; range, 36 to 77). Sixty-eight were head and neck patients treated by a 5-day continuous infusion of fluorouracil (FU; starting dose, 1 g/m2/d, with dose adaptation based on pharmacokinetics) for which DPD activity was measured 2 to 3 days before FU administration (94 cycles analyzed). PMNC-DPD activity was measured by a radio-enzymatic assay using carbon-14-FU. RESULTS DPD activity in the entire population showed a unimodal distribution, which globally fits a gaussian distribution. Mean and median DPD activity values were 0.222 and 0.211 nmol/min/mg protein, respectively (range, 0.065 to 0.559). No total DPD deficiency was found. Multifactor analysis of variance showed that liver function (biologic evaluation) and age did not influence DPD activity, but that DPD activity was, on average, 15% lower in women (0.194 nmol/min/mg protein) than in men (0.228 nmol/min/mg protein) (P = .03). No difference was demonstrated between premenopausal and postmenopausal women. In patients treated with FU, the risk of developing side effects was not linked to pretreatment DPD activity. FU-related toxicity was linked to FU systemic exposure. The correlation between pretreatment DPD activity and FU systemic clearance (CI) was weak (n = 90, linear regression r = .31, P = .002). Pretreatment DPD activity in patients who required a dose reduction was not significantly different from DPD activity in patients who did not require dose modification. CONCLUSION From the present study, it appears that total DPD deficiency is a rare event. Although pretreatment DPD activity cannot be a useful indicator for improving FU dose adaptation strategy, the identification of severe DPD deficiency (< 0.100 nmol/min/mg protein) could lead to starting the treatment with a markedly reduced FU dose or even to using an alternative chemotherapy regimen.

scholarly journals Tegafur–uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle

2012 ◽  
Vol 4 (4) ◽  
pp. 167-172 ◽  
Author(s):  
Daniel I.G. Cubero ◽  
Felipe Melo Cruz ◽  
Patrícia Santi ◽  
Ismael Dale C.G. Silva ◽  
Auro del Giglio
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Dehydrogenase Deficiency ◽  
Dihydropyrimidine Dehydrogenase ◽  
Gene Sequencing ◽  
Severe Toxicity ◽  
Safe Alternative ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Proof Of Principle

Objective: The objective of this study was to evaluate the safety of using tegafur–uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency. Patients and Methods: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m2/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle. Results: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea). Conclusion: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.

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